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μ opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis
Open accessAbstract
Several studies have described functional interactions between opioid and cannabinoid receptors; the underlying mechanism(s) have not been well explored. One possible mechanism is direct receptor–receptor interactions, as has been demonstrated for a number of G‐protein‐coupled receptors. In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged μ, δ and κ opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid–cannabinoid interactions are receptor specific. In order to examine the implications of these interactions to signaling, we used GTP γ S binding and mitogen‐activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. We find that the μ receptor‐mediated signaling is attenuated by the CB1 receptor agonist; this effect is reciprocal and is seen in heterologous cells and endogenous tissue expressing both receptors. In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro‐2A cells. We find that the simultaneous activation of μ opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor–receptor interactions in modulating neuritogenesis. British Journal of Pharmacology (2006) 148, 387–395. doi:10.1038/sj.bjp.0706757
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“Of importance, these receptors share similar signal transduction pathways (Rios et al, 2006).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rios et al, 2006
In the citing paper
“In addition to the above described influence of the CB 1 receptor on neuronal dynorphin release, CB 1 receptors and MORs form heterodimers, which account for enhanced neuronal antinociceptive interactions of cannabinoids and opioids (Rios et al, 2006).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Rios et al, 2006
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Cites
Ledent, C. A., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Impérato, A., Pedrazzini, T., Roques, B. P., et al. (1999) · Science · doi:10.1126/science.283.5400.401 · Cited by 3,618
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., Felder, C. C., Herkenham, M., Mackie, K., Martin, B. R., et al. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.161 · Cited by 2,819
Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor
KUNISHIMA, N., Shimada, Y., Tsuji, Y., Sato, T., Yamamoto, M., Kumasaka, T., Nakanishi, S., Jingami, H., & Morikawa, K. (2000) · Nature · doi:10.1038/35039564 · Cited by 1,249
Heterodimerization is required for the formation of a functional GABAB receptor
White, J. H. M., Wise, A., Main, M. J., Green, A., Fraser, N. J., Disney, G. H., Barnes, A. A., Emson, P. C., Foord, S. M., & Marshall, F. H. (1998) · Nature · doi:10.1038/25354 · Cited by 1,165
International Union of Pharmacology. XII. Classification of opioid receptors
Bn, D., Cesselin, F., Raghubir, R., Reisine, T., Bradley, P. B., Portoghese, P. S., & Hamon, M. (1996) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06958-3 · Cited by 732
Dimerization: An Emerging Concept for G Protein–Coupled Receptor Ontogeny and Function
Angers, S., Salahpour, A., & Bouvier, M. (2002) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.091701.082314 · Cited by 586
Pharmacological and biochemical interactions between opioids and cannabinoids
Manzanares, J., Corchero, J., Romero, J., Fernández‐Ruíz, J., Ramos, J. A., & Fuentes, J. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01339-5 · Cited by 391
A role for heterodimerization of μ and δ opiate receptors in enhancing morphine analgesia
Gomes, I., Gupta, A., Filipovska, J., Szeto, H. H., Pintar, J. E., & Devi, L. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307601101 · Cited by 386
Self-citationRodriguez, J. J., Mackie, K., & Pickel, V. M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-03-00823.2001 · Cited by 372
Jordan, B. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.011384898 · Cited by 328
G-protein-coupled receptor dimerization: modulation of receptor function
Rios, C., Jordan, B. A., Gomes, I., & Devi, L. A. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00160-7 · Cited by 309
Self-citationSynergistic interactions between cannabinoid and opioid analgesics
Cichewicz, D. L. (2004) · Life Sciences · doi:10.1016/j.lfs.2003.09.038 · Cited by 305
The Fourth Transmembrane Segment Forms the Interface of the Dopamine D2 Receptor Homodimer
Guo, W. X., Shi, L., & Javitch, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200679200 · Cited by 296
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity
Kniazeff, J., Bessis, A., Maurel, D., Ansanay, H., Prézeau, L., & Pin, J. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb794 · Cited by 290
Guo, W. X., Shi, L., Filizola, M., Weinstein, H., & Javitch, J. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508950102 · Cited by 290
Banères, J., & Parello, J. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00439-x · Cited by 275
Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors
Ghozland, S. G., Matthes, H. W. D., Simonin, F., Filliol, D., Kieffer, B. L., & Maldonado, R. J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-01146.2002 · Cited by 272
Pickel, V. M., Chan, J., Kash, T. L., Rodrı́guez, J.-J., & Mackie, K. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.015 · Cited by 243
Redistribution of GABA B(1) Protein and Atypical GABA B Responses in GABA B(2) -Deficient Mice
Gassmann, M., Shaban, H., Vigot, R., Sansig, G., Haller, C., Barbieri, S., Humeau, Y., Schuler, V., Müller, M., Kinzel, B., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5635-03.2004 · Cited by 228
The G protein‐coupled receptor rhodopsin in the native membrane
Fotiadis, D., Liang, Y., Filipek, S., Saperstein, D. A., Engel, A. H., & Palczewski, K. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00194-2 · Cited by 227
Solinas, M., Panlilio, L. V., Antoniou, K., Pappas, L., & Goldberg, S. R. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.047928 · Cited by 194
Filipek, S., Krzyśko, K. A., Fotiadis, D., Liang, Y., Saperstein, D. A., Engel, A. H., & Palczewski, K. (2004) · Photochemical & Photobiological Sciences · doi:10.1039/b315661c · Cited by 174
Functional Interactions between μ Opioid and α2A-Adrenergic Receptors
Jordan, B. A., Gomes, I., Rios, C., Filipovska, J., & Devi, L. A. (2003) · Molecular Pharmacology · doi:10.1124/mol.64.6.1317 · Cited by 173
Self-citationCB1-cannabinoid and μ-opioid receptor co-localization on postsynaptic target in the rat dorsal horn
Salio, C., Fischer, J., Franzoni, M. F., Mackie, K., Kaneko, T., & Conrath, M. (2001) · Neuroreport · doi:10.1097/00001756-200112040-00017 · Cited by 159
Vásquez, C., & Lewis, D. L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09271.1999 · Cited by 148
Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an example
Wager‐Miller, J., Westenbroek, R. E., & Mackie, K. (2002) · Chemistry and Physics of Lipids · doi:10.1016/s0009-3084(02)00151-2 · Cited by 144
Serotonin receptor activation leads to neurite outgrowth and neuronal survival
Fricker, A. D., Rios, C., Devi, L. A., & Gomes, I. (2005) · Molecular Brain Research · doi:10.1016/j.molbrainres.2005.04.016 · Cited by 139
Self-citationJordan, J. D., He, J. C., Eungdamrong, N. J., Gomes, I., Ali, W., Nguyen, T., Bivona, T. G., Philips, M. R., Devi, L. A., & Iyengar, R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411521200 · Cited by 130
Self-citationRubino, T., Viganò, D., Massi, P., & Parolaro, D. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0752080.x · Cited by 108
He, C., Gomes, I., Nguyen, T., Jayaram, G., Ram, P. T., Devi, L. A., & Iyengar, R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502812200 · Cited by 107
Self-citationModulation of rat brain opioid receptors by cannabinoids.
VAYSSE, P. J. ‐., Gardner, E. L., & Zukin, R. S. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-5347(25)00276-9 · Cited by 102
Oligomerization of opioid receptors
Gomes, I., Filipovska, J., Jordan, B. A., & Devi, L. A. (2002) · Methods · doi:10.1016/s1046-2023(02)00094-4 · Cited by 96
Self-citationNair, V. D., & Sealfon, S. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303364200 · Cited by 93
Allosteric modulators of G-protein-coupled receptors
May, L. T. (2003) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(03)00107-3 · Cited by 84
Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines
Nair, V. D., Olanow, C. W., & Sealfon, S. C. (2003) · Biochemical Journal · doi:10.1042/bj20030017 · Cited by 78
Xiao, J., & Liu, Y. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01961.x · Cited by 56
Zhao, W., Alkon, D. L., & Ma, W. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10591 · Cited by 54
INTERACTIONS BETWEEN δ OPIOID RECEPTORS AND α2A‐ADRENOCEPTORS
Rios, C., Gomes, I., & Devi, L. A. (2004) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2004.04076.x · Cited by 38
Self-citationFunctional Interactions between Opioid and 2A -Adrenergic Receptors
Jordan, B. A., Gomes, I., Rios, C., Filipovska, J., & Devi, L. A. (2003) · Cited by 35
Self-citationDelta opioid receptor in human neuroblastoma cell lines
Hochhaus, G., Yu, V. C. K., & Sadée, W. (1986) · Brain Research · doi:10.1016/0006-8993(86)91341-7 · Cited by 22
Gomes, I., Gupta, A., Singh, S. P., & Sharma, S. K. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00878-9 · Cited by 12
Self-citationInteraction of opioid drugs with human platelet α2-adrenoceptors
Ballesta, J. J., & Orts, A. (1992) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(92)90015-n · Cited by 11
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Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. H., Marzo, V. D., Elphick, M. R., Greasley, P. J., Hansen, H. S., Kunos, G., Mackie, K., et al. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.003004 · Cited by 1,666
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Metadata
- Authors
- Rios, C., Gomes, I., & Devi, L. A.
- Affiliations
- Cornell University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Devi, Lakshmi A
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2006-06
- Volume
- 148
- Issue
- 4
- Pages
- 387-395
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1751792
- OpenAlex
- W1487872499
- Cited by
- 327
- References
- 42
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 13 · 2023: 7 · 2022: 10 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 15 · 2016: 16 · 2015: 9 · 2014: 18 · 2013: 21 · 2012: 25
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DA08863)
- National Institute on Drug Abuse (DA 08863, K05DA019521, R56DA008863, R37DA008863, DA19521, R01DA008863)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- mu-opioid receptor, CB1 receptor, receptor-receptor interactions, opioid-cannabinoid interaction, neurite outgrowth, bioluminescence resonance energy transfer, CCR5 chemokine receptor, MAPK phosphorylation, Src phosphorylation, STAT3 phosphorylation, N2a cells
- MeSH terms
- Cells, Cultured, Humans, Phosphorylation, Signal Transduction, Guanosine 5'-O-(3-Thiotriphosphate), Neurites, Receptors, Opioid, mu, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Receptor, Cannabinoid, CB1, Extracellular Signal-Regulated MAP Kinases
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