A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases
Abstract
Previous studies in our laboratory have shown that in NIH3T3-5HT2A cells, 5-HT-induced AA release is PLA2-coupled and independent of 5-HT2A receptor-mediated PLC activation. Although 5-HT2A receptor-mediated PLC activation is known to be Galphaq-coupled, much less is understood about 5-HT2A receptor-mediated PLA2 activation. Therefore, the studies presented here were aimed at elucidating the signal transduction pathway linking stimulation of the 5-HT2A receptor to PLA2 activation. By employing various selective inhibitors, toxins, and antagonistic peptide constructs, we propose that the 5-HT2A receptor can couple to PLA2 activation through two parallel signaling cascades. Initial experiments were designed to examine the role of pertussis toxin-sensitive G proteins, namely Galphai/o, as well as pertussis toxin-insensitive G proteins, namely Galpha12/13, in 5-HT-induced AA release. Furthermore, inactivation of both Gbetagamma heterodimers and Rho proteins resulted in decreased agonist-induced AA release, without having any effect on PLC-IP accumulation. We also demonstrated 5-HT2A receptor-mediated phosphorylation of ERK1,2 and p38. Moreover, pretreatment with selective ERK1,2 and p38 inhibitors resulted in decreased 5-HT-induced AA release. Taken together, these results suggest that the 5-HT2A receptor expressed in NIH3T3 cells can couple to PLA2 activation though a complex signaling mechanism involving both Galphai/o-associated Gbetagamma-mediated ERK1,2 activation and Galpha12/13-coupled, Rho-mediated p38 activation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Via activation of 5-HT2AR, psychedelics activate intracellular signaling pathways such as PLC, PLA, and Src.
“Via activation of 5-HT2AR, psychedelics activate intracellular signaling pathways such as PLC, PLA, and Src (88–90).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [88]
Cites
International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).
Hoyer, D., Clarke, D. E., Fozard, J. R., Hartig, P. R., Martin, G. R., Mylecharane, E. J., Saxena, P. R., & Humphrey, P. P. A. (1994) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06783-3 · Cited by 2,997 · see citing works
Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P., & Irvine, R. F. (1983) · Biochemical Journal · doi:10.1042/bj2120473 · Cited by 1,954 · see citing works
cPLA2 is phosphorylated and activated by MAP kinase
Lin, L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A., & Davis, R. J. (1993) · Cell · doi:10.1016/0092-8674(93)90666-e · Cited by 1,851 · see citing works
Clark, J. D., Lin, L.-L., Kriz, R. W., Ramesha, C. S., Sultzman, L. A., Lin, A. Y., Milona, N., & Knopf, J. L. (1991) · Cell · doi:10.1016/0092-8674(91)90556-e · Cited by 1,688 · see citing works
Katada, T., & Ui, M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.10.3129 · Cited by 811 · see citing works
Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Gα 13
Hart, M. J., Jiang, X., Kozasa, T., Roscoe, W., Singer, W. D., Gilman, A. G., Sternweis, P. C., & Bollag, G. E. (1998) · Science · doi:10.1126/science.280.5372.2112 · Cited by 780 · see citing works
Regulatory Functions of Phospholipase A2
Murakami, M., Nakatani, Y., Atsumi, G., Inoue, K., & Kudo, I. (1997) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v17.i3-4.10 · Cited by 542 · see citing works
Sekine, A., Fujiwara, M., & Narumiya, S. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81834-8 · Cited by 541 · see citing works
Nemenoff, R. A., Winitz, S., Qian, N. X., Putten, V. V., Johnson, G. L., & Heasley, L. E. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53948-x · Cited by 522 · see citing works
Clark, J., Schievella, A., Nalefski, E. A., & Lin, L. (1995) · Journal of Lipid Mediators and Cell Signalling · doi:10.1016/0929-7855(95)00012-f · Cited by 515 · see citing works
Berg, K. A., Maayani, S., Goldfarb, J., Scaramellini, C., Leff, P., & Clarke, W. P. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.1.94 · Cited by 512 · see citing works
Gβγ Subunits Mediate Src-dependent Phosphorylation of the Epidermal Growth Factor Receptor
Luttrell, L. M., Rocca, G. J. D., van Biesen, T., Luttrell, D. K., & Lefkowitz, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4637 · Cited by 457 · see citing works
Distinct Pathways of Gi- and Gq-mediated Mitogen-activated Protein Kinase Activation
Hawes, B. E., van Biesen, T., Koch, W. J., Luttrell, L. M., & Lefkowitz, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17148 · Cited by 455 · see citing works
Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2
Sharp, J., White, D. L., Chiou, X. G., Goodson, T. G., III, Gamboa, G. C., McClure, D. B., Burgett, S. G., Hoskins, J., Skatrud, P. L., & Sportsman, J. R. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98550-9 · Cited by 448 · see citing works
Burch, R. M., Luini, A., & Axelrod, J. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.19.7201 · Cited by 427 · see citing works
Burch, R. M., & Axelrod, J. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.18.6374 · Cited by 376 · see citing works
The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release
Murakami, M., Shimbara, S., Kambe, T., Kuwata, H., Winstead, M. V., Tischfield, J. A., & Kudo, I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14411 · Cited by 366 · see citing works
Balsinde, J., & Dennis, E. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.12.6758 · Cited by 353 · see citing works
Rho family proteins and Ras transformation: the RHOad less traveled gets congested
Zohn, I. M., Campbell, S. L., Khosravi-Far, R., Rossman, K. L., & Der, C. J. (1998) · Oncogene · doi:10.1038/sj.onc.1202181 · Cited by 352 · see citing works
The Role of Rho in G Protein-Coupled Receptor Signal Transduction
Sah, V. P., Seasholtz, T. M., Sagi, S. A., & Brown, J. H. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.459 · Cited by 348 · see citing works
Jelsema, C. L., & Axelrod, J. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.11.3623 · Cited by 341 · see citing works
Heptahelical Receptor Signaling: Beyond the G Protein Paradigm
Hall, R. A., Premont, R. T., & Lefkowitz, R. J. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.5.927 · Cited by 325 · see citing works
The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase
Wilson, K. P., McCaffrey, P. G., Hsiao, K., Pazhanisamy, S., Galullo, V., Bemis, G. W., Fitzgibbon, M. J., Caron, P. R., Murcko, M. A., & Su, M. S. S. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90194-0 · Cited by 275 · see citing works
Structure, function and regulation of Ca2+‐sensitive cytosolic phospholipase A2 (cPLA2)
Kramer, R. M., & Sharp, J. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00322-0 · Cited by 255 · see citing works
Felder, C. C., Kanterman, R. Y., Ma, A. L., & Axelrod, J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.6.2187 · Cited by 220 · see citing works
Thrombin Induces Activation of p38 MAP Kinase in Human Platelets
Kramer, R. M., Roberts, E. F., Strifler, B. A., & Johnstone, E. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27395 · Cited by 213 · see citing works
Role of Phosphorylation Sites and the C2 Domain in Regulation of Cytosolic Phospholipase A2
Gijón, M. A., Spencer, D. M., Kaiser, A. L., & Leslie, C. C. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.6.1219 · Cited by 207 · see citing works
Xu, N., Bradley, L., Ambdukar, I., & Gutkind, J. S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6741 · Cited by 176 · see citing works
Kurrasch‐Orbaugh, D. M., Watts, V. J., Barker, E. L., & Nichols, D. E. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.042184 · Cited by 166 · see citing works
Self-citationKatoh, H., Aoki, J., Yamaguchi, Y., Kitano, Y., Ichikawa, A., & Negishi, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28700 · Cited by 165 · see citing works
Communal, C., Colucci, W. S., & Singh, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910471199 · Cited by 164 · see citing works
Hernández, M., Burillo, S., Crespo, M. S., & Nieto, M. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.606 · Cited by 156 · see citing works
Signaling by the G Class of G Proteins
Dhanasekaran, N., & Dermott, J. M. (1996) · Cellular Signalling · doi:10.1016/0898-6568(96)00048-4 · Cited by 143 · see citing works
Signal transduction differences between 5-hydroxytryptamine type 2A and type 2C receptor systems.
Berg, K. A., Clarke, W. P., Sailstad, C. A., Saltzman, A. G., & Maayani, S. (1994) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09724-x · Cited by 134 · see citing works
Murakami, M., Nakatani, Y., & Kudo, I. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30041 · Cited by 132 · see citing works
Mammalian phospholipases A2: mediators of inflammation, proliferation and apoptosis
Capper, E. A., & Marshall, L. A. (2001) · Progress in Lipid Research · doi:10.1016/s0163-7827(01)00002-9 · Cited by 129 · see citing works
Fonteh, A. N., Bass, D., Marshall, L. A., Seeds, M. C., Samet, J. M., & Chilton, F. H. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.11.5438 · Cited by 129 · see citing works
Neve, R. L., Howe, J. R., Hong, S. E., & Kalb, R. G. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00645-8 · Cited by 124 · see citing works
Watts, S. W. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21317-9 · Cited by 121 · see citing works
Mao, J., Yuan, H., Xie, W., & Wu, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.12973 · Cited by 121 · see citing works
A G Protein Mutant That Inhibits Thrombin and Purinergic Receptor Activation of Phospholipase A 2
Gupta, S., Dı́ez, E., Heasley, L. E., Osawa, S., & Johnson, G. L. (1990) · Science · doi:10.1126/science.2166341 · Cited by 109 · see citing works
Cross-talk between 5-Hydroxytryptamine Receptors in a Serotonergic Cell Line
Tournois, C., Mutel, V., Manivet, P., Launay, J., & Kellermann, O. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17498 · Cited by 102 · see citing works
Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis
Kelleher, M. D., Abe, M. K., Chao, T. S., Jain, M. K., Green, J. M., Solway, J., Rosner, M. R., & Hershenson, M. B. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.268.6.l894 · Cited by 89 · see citing works
Ghahremani, M. H., Cheng, P., Lembo, P. M. C., & Albert, P. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.14.9238 · Cited by 88 · see citing works
Florian, J. A., & Watts, S. W. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37202-7 · Cited by 82 · see citing works
Mansour, S. J., Candia, J. M., Gloor, K. K., & Ahn, N. G. (1996) · PubMed · Cited by 64 · see citing works
Structure of the rgRGS domain of p115RhoGEF.
Chen, Z., Wells, C. D., Sternweis, P. C., & Sprang, S. R. (2001) · Nature Structural Biology · doi:10.1038/nsb0901-805 · Cited by 57 · see citing works
Cytokine‐mediated cPLA2 phosphorylation is regulated by multiple MAPK family members
Geijsen, N., Dijkers, P. F., Lammers, J. J., Koenderman, L., & Coffer, P. J. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01373-9 · Cited by 52 · see citing works
SELBIE, A. L., King, N. V., Dickenson, J. M., & Hill, S. J. (1997) · Biochemical Journal · doi:10.1042/bj3280153 · Cited by 50 · see citing works
Yamauchi, J., Tsujimoto, G., Kaziro, Y., & Itoh, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011752200 · Cited by 40 · see citing works
Nuclear signalling by Rac GTPase: essential role of phospholipase A2
Kim, B.-C., & Kim, J. (1997) · Biochemical Journal · doi:10.1042/bj3260333 · Cited by 33 · see citing works
Yoo, M.-H., Woo, C.-H., You, H. J., Cho, S.-H., Byung-Chul, K. I. M., Choi, J. E., Chun, J. S., Jhun, B. H., Kim, T. S., & Kim, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101975200 · Cited by 28 · see citing works
Oncogenic mutant of Gα12 stimulates cell proliferation through cycloxygenase-2 signaling pathway
Dermott, J. M., Reddy, M. R., Onésime, D., Reddy, E. P., & Dhanasekaran, N. (1999) · Oncogene · doi:10.1038/sj.onc.1203345 · Cited by 27 · see citing works
Sa, G., & Das, T. (1999) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006970710298 · Cited by 24 · see citing works
Cooperative transformation of NIH3T3 cells by Gα12 and Rac1
Tolkacheva, T., Feuer, B., Lorenzi, M. V., Sáez, R., & Chan, A. M.-L. (1997) · Oncogene · doi:10.1038/sj.onc.1201229 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nichols, D. E. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011478 · Cited by 1,762 · see citing works
Self-citationNichols, D. E. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2003.11.002 · Cited by 1,211 · see citing works
Self-citationFunctional Selectivity and Classical Concepts of Quantitative Pharmacology
Urban, J. D., Clarke, W. P., von Zastrow, M., Nichols, D. E., Kobilka, B. K., Weinstein, H., Javitch, J. A., Roth, B. L., Christopoulos, A., Sexton, P. M., et al. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.104463 · Cited by 1,119 · see citing works
Self-citationGonzález-Maeso, J., Weisstaub, N. V., Zhou, M., Chan, P., Ivic, L., Ang, R., Lira, A., Bradley-Moore, M., Ge, Y., Zhou, Q., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.008 · Cited by 925 · see citing works
Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases.
Sun, G. Y., Xu, J.-F., Jensen, M. D., & Simonyi, Á. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300016-jlr200 · Cited by 378 · see citing works
The role of serotonin 5-HT2A receptors in memory and cognition
Zhang, G., & Stackman, R. W. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00225 · Cited by 386 · see citing works
Farooqui, A. A., Ong, W., & Horrocks, L. A. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.7 · Cited by 368 · see citing works
Recent advances in the neuropsychopharmacology of serotonergic hallucinogens
Halberstadt, A. L. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.07.016 · Cited by 312 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript and p38 MAP kinase), Akt, and phospholipase D (dependent on the small G protein ADPribosylation factor-1 (ARF1)) (Kurrasch-Orbaugh et al., 2003a; González-Maeso et al., 2007; Schmid and Bohn, 2010; Barclay et al., 2011).”
BackgroundInfluentialPlatelets and cancer: a casual or causal relationship: revisited
Menter, D. G., Tucker, S. C., Kopetz, S., Sood, A. K., Crissman, J. D., & Honn, K. V. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9498-0 · Cited by 317 · see citing works
The neural basis of psychedelic action
Kwan, A. C., Olson, D. E., Preller, K. H., & Roth, B. L. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01177-4 · Cited by 312 · see citing works
Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways
López‐Giménez, J. F., & González‐Maeso, J. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_478 · Cited by 311 · see citing works
de Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.724606 · Cited by 269 · see citing works
Barnes, N. M., Ahern, G. P., Bécamel, C., Bockaert, J., Camilleri, M., Chaumont‐Dubel, S., Claeysen, S., Cunningham, K. A., Fone, K. C. F., Gershon, M. D., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.118.015552 · Cited by 264 · see citing works
Moreno, J. L., Holloway, T. D., Albizu, L., Sealfon, S. C., & González‐Maeso, J. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.01.046 · Cited by 235 · see citing works
Agonist-directed signaling of the serotonin 2A receptor depends on β-arrestin-2 interactions in vivo
Schmid, C. L., Raehal, K. M., & Bohn, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708862105 · Cited by 231 · see citing works
Functions of 5-HT2A receptor and its antagonists in the cardiovascular system
Nagatomo, T., Rashid, M., Muntasir, H. A., & Komiyama, T. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.08.005 · Cited by 186 · see citing works
Schmid, C. L., & Bohn, L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-10.2010 · Cited by 176 · see citing works
Seyedabadi, M., Ghahremani, M. H., & Albert, P. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.006 · Cited by 148 · see citing works
Lipid agonism: The PIP2 paradigm of ligand-gated ion channels
Hansen, S. B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.01.011 · Cited by 146 · see citing works
Kelly, P., Casey, P. J., & Meigs, T. E. (2007) · Biochemistry · doi:10.1021/bi700235f · Cited by 136 · see citing works
Serotonergic signaling: multiple effectors and pleiotropic effects
Masson, J., Emerit, M. B., Hamon, M., & Darmon, M. C. (2012) · Wiley Interdisciplinary Reviews Membrane Transport and Signalling · doi:10.1002/wmts.50 · Cited by 132 · see citing works
Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity
Olson, D. E. (2022) · Biochemistry · doi:10.1021/acs.biochem.1c00812 · Cited by 135 · see citing works
How serotonin receptors regulate morphogenic signalling in neurons
Wirth, A., Holst, K., & Ponimaskin, E. G. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.03.007 · Cited by 122 · see citing works
Knock, G. A. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.09.029 · Cited by 108 · see citing works
Xia, Y., Fu, Z., Hu, J., Huang, C. Y., Paudel, O., Cai, S., Liedtke, W., & Sham, J. S. K. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00099.2013 · Cited by 108 · see citing works
On the analysis of ligand-directed signaling at G protein-coupled receptors
Ehlert, F. J. (2008) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-008-0260-4 · Cited by 94 · see citing works
Duan, W., Cao, D., Wang, S., & Cheng, J. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00375 · Cited by 79 · see citing works
Garcia, E. E., Smith, R. L., & Sanders‐Bush, E. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.03.013 · Cited by 78 · see citing works
The role of phospholipases A2 in schizophrenia
Law, M. H., Cotton, R. G. H., & Berger, G. E. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001819 · Cited by 72 · see citing works
Parrish, J. C., & Nichols, D. E. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04173.x · Cited by 63 · see citing works
Self-citationNichols, C. D., & Sanders‐Bush, E. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02515.x · Cited by 62 · see citing works
Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
Kang, B., Ha, S., Bahaie, N. S., Hosseinkhani, M., Ge, X.-N., Blumenthal, M., Rao, S. P., & Sriramarao, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054840 · Cited by 56 · see citing works
PUFA and their derivatives in neurotransmission and synapses: a new hallmark of synaptopathies
Miceli, M. D., Bosch‐Bouju, C., & Layé, S. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120000129 · Cited by 56 · see citing works
Holze, F., Singh, N., Liechti, M., & D'Souza, D. (2024) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.01.007 · Cited by 44 · see citing works
Daniele, S., Pozzo, E. D., Zappelli, E., & Martini, C. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.04.006 · Cited by 55 · see citing works
Serotonin 2A (5-HT2A) Receptor Function: Ligand-Dependent Mechanisms and Pathways
Chattopadhyay, A. (2007) · CRC Press eBooks · doi:10.1201/9781420005752-11 · Cited by 56 · see citing works
The Effects of Hallucinogens on Gene Expression
Martin, D. A., & Nichols, C. D. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_479 · Cited by 51 · see citing works
Activation, internalization, and recycling of the serotonin 2A receptor by dopamine
Bhattacharyya, S., Raote, I., Bhattacharya, A., Miledi, R., & Panicker, M. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606578103 · Cited by 51 · see citing works
Wolf, G., Singh, S., Blakolmer, K., Lerer, L. A., Lifschytz, T., Heresco-Levy, U., Lotan, A., & Lerer, B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01832-z · Cited by 33 · see citing works
Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action
Canal, C. E. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_107 · Cited by 48 · see citing works
How much do we know about the coupling of G-proteins to serotonin receptors?
Giulietti, M., Vivenzio, V., Piva, F., Principato, G., Bellantuono, C., & Nardi, B. (2014) · Molecular Brain · doi:10.1186/s13041-014-0049-y · Cited by 46 · see citing works
Settimo, L., & Taylor, D. M. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881117742101 · Cited by 45 · see citing works
Govindula, A., Ranadive, N., Nampoothiri, M., Rao, C. M., Arora, D. S., & Mudgal, J. (2023) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-023-10064-z · Cited by 44 · see citing works
Structure–Activity Relationships of Phenylalkylamines as Agonist Ligands for 5‐HT2A Receptors
Blaazer, A. R., Smid, P., & Kruse, C. G. (2008) · ChemMedChem · doi:10.1002/cmdc.200800133 · Cited by 43 · see citing works
Boas, G. R. V., Lavorato, S. N., Paes, M. M., Galdino, P. M., Rescia, V. C., Cunha, M. S., de Magalhães-Filho, M. F., Ponsoni, L. F., de Carvalho, A. A. V., de Lacerda, R. B., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14020148 · Cited by 42 · see citing works
Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor
Gaitonde, S. A., Avet, C., Revenga, M. D. L. F., Blondel-Tepaz, É., Shahraki, A., Pastor, A. M., Talagayev, V., Robledo, P., Kolb, P., Selent, J., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02531-7 · Cited by 42 · see citing works
Peddie, C. J., Davies, H. A., Colyer, F. M., Stewart, M. G., & Rodríguez, J. J. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.03.003 · Cited by 39 · see citing works
Pottie, E., & Stove, C. P. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15570 · Cited by 37 · see citing works
Xiang, M., Jiang, Y., Hu, Z., Yang, Y., Du, X., Botchway, B. O. A., & Fang, M. (2019) · PubMed Central · Cited by 36 · see citing works
Oufkir, T., & Vaillancourt, C. (2011) · Placenta · doi:10.1016/j.placenta.2011.09.005 · Cited by 36 · see citing works
Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate
Jiménez, J. H., & Bouso, J. C. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221104054 · Cited by 37 · see citing works
Weinstein, H. (2005) · The AAPS Journal · doi:10.1208/aapsj070485 · Cited by 34 · see citing works
5-HT2A and mGlu2/3 receptor interactions
Wischhof, L., & Koch, M. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000183 · Cited by 33 · see citing works
Serum calcium‐independent phospholipase A2 activity in bipolar affective disorder
Ross, B. M., Hughes, B., Kish, S. J., & Warsh, J. J. (2006) · Bipolar Disorders · doi:10.1111/j.1399-5618.2006.00299.x · Cited by 33 · see citing works
The renaissance in psychedelic research: What do preclinical models have to offer
Murnane, K. S. (2018) · Progress in brain research · doi:10.1016/bs.pbr.2018.08.003 · Cited by 31 · see citing works
The crosstalk between 5-HT2AR and mGluR2 in schizophrenia
Saha, S., & González‐Maeso, J. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109489 · Cited by 30 · see citing works
Ősz, B.-E., Jîtcă, G., Sălcudean, A., Rusz, C.-M., & Vari, C.-E. (2023) · Pharmaceuticals · doi:10.3390/ph16040566 · Cited by 31 · see citing works
The evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity
Gupta, S., Bhatnagar, R. K., Gupta, D., Maharaj Kumari, K., & Chopra, A. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06777-z · Cited by 30 · see citing works
Valentín-Berríos, S., González-Velázquez, W., Pérez-Sánchez, L., Gonzalez-Mendez, R. R., & Valle, N. R.-D. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-100 · Cited by 30 · see citing works
Retamal, J. S., Grace, M. S., Dill, L. K., Ramírez-García, P. D., Peng, S., Gondin, A. B., Bennetts, F. M., Alvi, S., Rajasekhar, P., Almazi, J. G., et al. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00593-7 · Cited by 28 · see citing works
Song, J.-L., Zheng, S., He, R., Gui, L., Lin, M., & Sham, J. S. K. (2021) · Vascular Pharmacology · doi:10.1016/j.vph.2021.106860 · Cited by 27 · see citing works
Giovanni, G. D., & Deurwaerdère, P. D. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.10.004 · Cited by 25 · see citing works
Bhattacharjee, A. K., Chang, L., White, L., Bazinet, R. P., & Rapoport, S. I. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600290 · Cited by 25 · see citing works
Role of a small G protein Ras in cellular immune response of the beet armyworm, Spodoptera exigua
Lee, S., Shrestha, S. S., Surakasi, V. P., & Kim, Y. (2010) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2010.12.003 · Cited by 25 · see citing works
Serotonergic Suppression of Mouse Prefrontal Circuits Implicated in Task Attention
Tian, M. K., Schmidt, E. F., & Lambe, E. K. (2016) · eNeuro · doi:10.1523/eneuro.0269-16.2016 · Cited by 23 · see citing works
Chronic fluoxetine upregulates arachidonic acid incorporation into the brain of unanesthetized rats
Qu, Y., Chang, L., Klaff, J., Seemann, R., GREENSTEIN, D. K., & Rapoport, S. I. (2006) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2006.01.008 · Cited by 23 · see citing works
Cloëz-Tayarani, I., Kayyali, U. S., Fanburg, B. L., & Cavaillon, J. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.09.006 · Cited by 21 · see citing works
The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies
Low, Z. X. B., Ng, W. S., Lim, E. S. Y., Goh, B. H., & Kumari, Y. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111139 · Cited by 20 · see citing works
Psychedelics action and schizophrenia
Maćkowiak, M. (2023) · Pharmacological Reports · doi:10.1007/s43440-023-00546-5 · Cited by 16 · see citing works
5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail
Barclay, Z., Dickson, L., Robertson, D. N., Johnson, M. S., Holland, P. J., Rosie, R., Sun, L., Fleetwood‐Walker, S., Lutz, E. M., & Mitchell, R. (2011) · Biochemical Journal · doi:10.1042/bj20101844 · Cited by 20 · see citing works
The Gq and G12 Families of Heterotrimeric G Proteins Report Functional Selectivity
Zhang, L., Brass, L. F., & Manning, D. R. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.050906 · Cited by 18 · see citing works
Stahl, E. L., Elmslie, G., & Ellis, J. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.072991 · Cited by 18 · see citing works
Kleffens, M. D.-V., Zimmermann-Klemd, A. M., & Gründemann, C. (2023) · Molecules · doi:10.3390/molecules28247942 · Cited by 17 · see citing works
Arrate, I. M., Miranda-Azpiazu, P., Horrillo, I., Dı́ez-Alarcia, R., & Meana, J. J. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16368 · Cited by 18 · see citing works
Catlow, B. J., Jalloh, A., & Sanchez‐Ramos, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800212-4.00077-7 · Cited by 17 · see citing works
Natural Psychoplastogens As Antidepressant Agents
Benko, J., & Vranková, S. (2020) · Molecules · doi:10.3390/molecules25051172 · Cited by 16 · see citing works
McNamara, R. K., Szeszko, P. R., Smesny, S., Ikuta, T., DeRosse, P., Vaz, F. M., Milleit, B., Hipler, U., Wiegand, C., Hesse, J., et al. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.12.007 · Cited by 16 · see citing works
Murnane, K. S., Güner, O. F., Bowen, J. P., Rambacher, K. M., Moniri, N. H., Murphy, T. J., Daphney, C. M., Oppong‐Damoah, A., & Rice, K. C. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.04.003 · Cited by 15 · see citing works
Santini, M. A., Klein, A. B., El-Sayed, M., Ratner, C., Knudsen, G. M., Mikkelsen, J. D., & Aznar, S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.05.048 · Cited by 15 · see citing works
Mercier, F., Morin, C., Cloutier, M., Proteau, S., Rokach, J., Powell, W. S., & Rousseau, É. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00005.2004 · Cited by 15 · see citing works
Serotonin Modulation of Dorsoventral Hippocampus in Physiology and Schizophrenia
Kandilakis, C. L., & Papatheodoropoulos, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157253 · Cited by 14 · see citing works
Jastrzębski, M. K., Wójcik, P., Grudzińska, A., Andreozzi, G., Vetrò, T., Asim, A., Mudgal, A., Czapiński, J., Wróbel, T. M., Bartuzi, D., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.002 · Cited by 14 · see citing works
Soto, C. A., Shashack, M. J., Fox, R. G., Bubar, M. J., Rice, K. C., Watson, C. S., Cunningham, K. A., Gilbertson, S. R., & Anastasio, N. C. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00309 · Cited by 13 · see citing works
Martín‐Guerrero, S. M., Alonso-Batan, P., Iglesias, A., Cimadevila, M., Brea, J. M., Loza, M. I., Casado, P., Martín‐Oliva, D., Cutillas, P. R., González‐Maeso, J., et al. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114440 · Cited by 13 · see citing works
Bhattacharjee, A. K., Meister, L. M., Chang, L., Bazinet, R. P., White, L., & Rapoport, S. I. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.06.012 · Cited by 13 · see citing works
Angiotensin II stimulates fibronectin protein synthesis via a Gβγ/arachidonic acid-dependent pathway
Alexander, L. D., Ding, Y., Alagarsamy, S., & Cui, X.-L. (2014) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00094.2014 · Cited by 12 · see citing works
Cannabidiol and the corticoraphe circuit in post-traumatic stress disorder
Alexander, C., & Vasefi, M. (2021) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2021.08.001 · Cited by 11 · see citing works
Selectivity for G Protein or Arrestin-Mediated Signaling
Bohn, L. (2009) · The Receptors · doi:10.1007/978-1-60327-335-0_5 · Cited by 11 · see citing works
Serotonin 2C receptors are also important in head-twitch responses in male mice
Custodio, R. J. P., Ortiz, D. M., Lee, H. J., Sayson, L. V., Kim, M., Lee, Y. S., Kim, K., Cheong, J. H., & Kim, H. J. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06482-9 · Cited by 10 · see citing works
Serotonin 2A receptors and cannabinoids
Ibarra‐Lecue, I., Dı́ez-Alarcia, R., & Urigüen, L. (2021) · Progress in brain research · doi:10.1016/bs.pbr.2021.01.004 · Cited by 11 · see citing works
Fryc, M., Kluzik, D., Czopek, A., Jończyk, J., & Zagórska, A. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110622 · Cited by 9 · see citing works
Ranjbaran, M., Kianian, F., Kadkhodaee, M., Seifi, B., Ashabi, G., Akhondzadeh, F., Adelipour, M., Izad, M. H., & Abdolmohammadi, K. (2022) · PubMed Central · doi:10.22038/ijbms.2022.61860.13690 · Cited by 9 · see citing works
Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?
Qureshi, O., Cowley, J., Pegg, A., Cooper, A. J., Gordon, J., Brady, C., Belli, A., Butterworth, S., Upthegrove, R., Andrews, N., et al. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70138 · Cited by 10 · see citing works
Zulfiker, A. H. M., Hashimi, S. M., Good, D. M., Grice, I. D., & Wei, M. Q. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25627 · Cited by 8 · see citing works
Biased Signaling in Psychedelic Action
Wacker, D., & McCorvy, J. D. (2025) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-062124-012545 · Cited by 8 · see citing works
Pirenperone relieves the symptoms of fragile X syndrome in Fmr1 knockout mice
Kim, Y., Jeon, S. J., Gonzales, E. L., Shin, D., Remonde, C. G., Ahn, T., & Shin, C. Y. (2022) · Scientific Reports · doi:10.1038/s41598-022-25582-8 · Cited by 7 · see citing works
Psychedelics and Hallucinogens in Psychiatry: Finding New Pharmacological Targets
de Sousa, T. R., Rema, J., Machado, S. E. D. C., & Novais, F. (2021) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026621666211201145800 · Cited by 7 · see citing works
la Cour, C. M., Chaput, C., Touzard, M., & Millan, M. J. (2008) · Synapse · doi:10.1002/syn.20587 · Cited by 7 · see citing works
Roméo, B., Kervadec, E., Fauvel, B., Strika-Bruneau, L., Amirouche, A., Verroust, V., Piolino, P., & Benyamina, A. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111300 · Cited by 7 · see citing works
- Authors
- Kurrasch‐Orbaugh, D. M., Parrish, J. C., Watts, V. J., & Nichols, D. E.
- Affiliations
- Purdue University West Lafayette (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-07-21
- Volume
- 86
- Issue
- 4
- Pages
- 980-991
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1523962342
- Cited by
- 138
- References
- 56
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 9 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA 02189)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- phospholipase A2 activation, arachidonic acid release, mitogen-activated protein kinase, ERK1/2, p38 MAPK, Gα12/13, Gαi/o, Rho proteins, signal transduction, pertussis toxin
- MeSH terms
- Animals, Enzyme Activation, Enzyme Inhibitors, Fibroblasts, Inositol Phosphates, Type C Phospholipases, Phospholipases A, Receptors, Serotonin, Signal Transduction, 3T3 Cells, Arachidonic Acid, GTP-Binding Proteins, Mitogen-Activated Protein Kinase 1, Enzyme Activators, rho GTP-Binding Proteins, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Receptor, Serotonin, 5-HT2A, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice, Phospholipases A2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review