Prominence of the dopamine D2 short isoform in dopaminergic pathways
Open accessAbstract
As a result of alternative splicing, the D2 gene of the dopamine receptor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is absent in the short isoform. We have produced subtype-specific antibodies against both the D2 short and D2 long isoforms and found a unique compartmentalization between these two isoforms in the primate brain. The D2 short predominates in the cell bodies and projection axons of the dopaminergic cell groups of the mesencephalon and hypothalamus, whereas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. These results show that the splice variants of the dopamine D2 receptor are differentially distributed and possess distinct functions. The strategic localization of the D2 short isoform in dopaminergic cell bodies and axons strongly suggests that this isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is primarily a postsynaptic receptor.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
These negative feedback mechanisms are mediated by somato-dendritic D2/D3 autoreceptors located on midbrain dopamine neurons, which play a key role in regulating dopamine synthesis and release by acting as potent inhibitors in the presence of high dopamine concentrations.
“These negative feedback mechanisms are mediated by somato-dendritic D2/D3 autoreceptors located on midbrain dopamine neurons, which play a key role in regulating dopamine synthesis and release by acting as potent inhibitors in the presence of high dopamine concentrations (Mercuri et al., 1992, 1997; Sesack et al., 1994; Khan et al., 1998).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Khan et al., 1998
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gerfen, C. R., Engber, T. M., Mahan, L. C., Susel, Z., Chase, T. N., Monsma, F. J., & Sibley, D. R. (1990) · Science · doi:10.1126/science.2147780 · Cited by 2,967 · see citing works
Parent, A., & Hazrati, L. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00008-d · Cited by 1,351 · see citing works
Alternative splicing directs the expression of two D2 dopamine receptor isoforms
Bruno Giros, A., Sokoloff, P., Martres, M., Riou, J., Emorine, L. J., & Schwartz, J.-C. (1989) · Nature · doi:10.1038/342923a0 · Cited by 685 · see citing works
Multiple D2 dopamine receptors produced by alternative RNA splicing
Monsma, F. J., McVittie, L. D., Gerfen, C. R., Mahan, L. C., & Sibley, D. R. (1989) · Nature · doi:10.1038/342926a0 · Cited by 641 · see citing works
A rapid filtration assay for soluble receptors using polyethylenimine-treated filters
Bruns, R. F., Lawson-Wendling, K. L., & Pugsley, T. A. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90427-x · Cited by 575 · see citing works
Nordström, A., Farde, L., Wiesel, F., Forslund, K., Pauli, S., Halldin, C., & Uppfeldt, G. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90288-o · Cited by 527 · see citing works
Localization of dopamine D4 receptors in GABAergic neurons of the primate brain
Mrzljak, L., Bergson, C., Pappy, M., Huff, R., Levenson, R., & Goldman-Rakic, P. S. (1996) · Nature · doi:10.1038/381245a0 · Cited by 494 · see citing works
Self-citationHersch, S. M., Ciliax, B. J., Gutekunst, C., Rees, H., Heilman, C. J., Yung, K. K. L., Bolam, J. P., Ince, E., Yi, H. L., & Levey, A. I. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-07-05222.1995 · Cited by 483 · see citing works
Sesack, Sr., Aoki, C., & Pickel, V. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-01-00088.1994 · Cited by 461 · see citing works
Kelly, M. A., Rubinstein, M., Asa, S. L., Zhang, G., Sáez, C., Bunzow, J. R., Allen, R. G., Hnasko, R. M., Ben‐Jonathan, N., Grandy, D. K., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80351-7 · Cited by 425 · see citing works
The Cortical Dopamine System: Role in Memory and Cognition
Goldman, P. S. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60846-7 · Cited by 393 · see citing works
Synaptic regulation of mesocorticolimbic dopamine neurons
White, F. J. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.19.030196.002201 · Cited by 289 · see citing works
Abnormal Synaptic Plasticity in the Striatum of Mice Lacking Dopamine D2 Receptors
Calabresi, P., Saiardi, A., Pisani, A., Baik, J., Centonze, D., Mercuri, N. B., Bernardi, G., & Borrelli, E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04536.1997 · Cited by 287 · see citing works
Williams, S. M., & Goldman-Rakic, P. S. (1993) · Cerebral Cortex · doi:10.1093/cercor/3.3.199 · Cited by 284 · see citing works
Self-citationNeve, K. A., & Neve, R. L. (1997) · Humana Press eBooks · doi:10.1007/978-1-4757-2635-0 · Cited by 259 · see citing works
Koeltzow, T. E., Xu, M., Cooper, D., Hu, X., Tonegawa, S., Wolf, M. E., & White, F. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02231.1998 · Cited by 234 · see citing works
Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome
Harris, G. C., & Aston‐Jones, G. (1994) · Nature · doi:10.1038/371155a0 · Cited by 214 · see citing works
Mercuri, N. B., Saiardi, A., Bonci, A., Picetti, R., Calabresi, P., Bernardi, G., & Borrelli, E. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00135-8 · Cited by 198 · see citing works
Cragg, S. J., & Greenfield, S. A. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05738.1997 · Cited by 184 · see citing works
Lidow, M. S., & Goldman‐Rakic, P. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4353 · Cited by 174 · see citing works
Self-citationLinking the Family of D2 Receptors to Neuronal Circuits in Human Brain: Insights into Schizophrenia
Joyce, J. N. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00276-x · Cited by 123 · see citing works
Increased abundance of alternatively spliced forms of D2 dopamine receptor mRNA after denervation.
Neve, K. A., Neve, R. L., Fidel, S., Janowsky, A. J., & Higgins, G. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.7.2802 · Cited by 101 · see citing works
Solubilisation of high-affinity dopamine receptors
Gorissen, H. J., & Laduron, P. M. (1979) · Nature · doi:10.1038/279072a0 · Cited by 72 · see citing works
Short and Long Form γ2 Subunits of the GABAA/Benzodiazepine Receptors
Khan, Z. U., Gutiérrez, A., & Blas, A. L. D. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63041466.x · Cited by 66 · see citing works
Self-citationRegulation of Dopamine D1 and D2 Receptors on Striatal Acetylcholine Release in Rats
Ikarashi, Y., Takahashi, A., Ishimaru, H., et al. (1997) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00351-6 · Cited by 60 · see citing works
Antibodies to the Human γ2 Subunit of the γ‐Aminobutyric AcidA/Benzodiazepine Receptor
Khan, Z. U., Fernando, L. P., Escribá, P. V., et al. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03243.x · Cited by 47 · see citing works
Self-citationSnyder, L., Roberts, J. L., & Sealfon, S. C. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90187-x · Cited by 41 · see citing works
Evidence that excitatory amino acids mediate afferent input to the primate somatosensory thalamus
Dougherty, P. M., Li, Y.-J., Lenz, F. A., et al. (1996) · Brain Research · doi:10.1016/0006-8993(96)00550-1 · Cited by 30 · see citing works
Dopamine receptors and schizophrenia
Reynolds, G. P. (1996) · Biochemical Society Transactions · doi:10.1042/bst0240202 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [2]Reynolds, J. P. (1996) Biochem. Soc. Trans. 24, 202-205.
- [18]Neve, K. A., Neve, R. L., Fidel, S., Janowski, A. & Higgins, G. A. (1991) Proc. Natl. Acad. Sci. USA 88, 2802-2806.
- [24]Lidow, M. S. & Goldman-Rakic, P. S. (1994) Proc. Natl. Acad. Sci. USA 91, 4353-4356.
Cited by
Sorted by citations
Distinct functions of the two isoforms of dopamine D2 receptors
Usiello, A., Baik, J.-H., Rougé-Pont, F., Picetti, R., Dierich, A., LeMeur, M., Piazza, P. V., & Borrelli, E. (2000) · Nature · doi:10.1038/35041572 · Cited by 717 · see citing works
Association of Multiple DRD2 Polymorphisms with Anorexia Nervosa
Bergen, A. W., Yeager, M., Welch, R. A., Haque, K., Ganjei, J. K., van den Bree, M. B. M., Mazzanti, C., Nardi, I., Fichter, M. M., Halmi, K. A., et al. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300719 · Cited by 137 · see citing works
Kaalund, S. S., Newburn, E. N., Ye, T., Tao, R., Li, C., Deep-Soboslay, A., Herman, M. M., Hyde, T. M., Weinberger, D. R., Lipska, B. K., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.165 · Cited by 132 · see citing works
Mottola, D. M., Kilts, J. D., Lewis, M. M., Connery, H. S., Walker, Q. D., Jones, S. R., Booth, R. G., Hyslop, D. K., Piercey, M., Wightman, R. M., et al. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.301.3.1166 · Cited by 123 · see citing works
Peciña, M., Mickey, B. J., Love, T., Wang, H., Langenecker, S. A., Hodgkinson, C., Shen, P.-H., Villafuerte, S., Hsu, D., Weisenbach, S. L., et al. (2013) · Cortex · doi:10.1016/j.cortex.2012.01.010 · Cited by 123 · see citing works
del Campo, N., Fryer, T. D., Hong, Y. T., Smith, R., Brichard, L., Acosta-Cabronero, J., Chamberlain, S. R., Tait, R., Izquierdo, D., Regenthal, R., et al. (2013) · Brain · doi:10.1093/brain/awt263 · Cited by 113 · see citing works
Feltmann, K., Borroto‐Escuela, D. O., Rüegg, J., Pinton, L., de Oliveira Sergio, T., Narváez, M., Jimenez‐Beristain, A., Ekström, T. J., Fuxe, K., & Steensland, P. (2018) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13568 · Cited by 67 · see citing works
- Authors
- Khan, Z. U., Mrzljak, L., Gutierrez, A., de la Calle, A., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510; and Department of Cell Biology, University of Malaga, Malaga 29071, Spain
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-06-23
- Volume
- 95
- Issue
- 13
- Pages
- 7731-7736
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22740
- OpenAlex
- W2032223397
- Cited by
- 278
- References
- 29
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 13 · 2019: 10 · 2018: 4 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 18 · 2012: 14
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine D2 receptor, alternative splicing, splice variants, dopaminergic pathways, dopamine autoreceptors, postsynaptic dopamine receptors, striatum, nucleus accumbens, midbrain, hypothalamus, receptor localization
- MeSH terms
- Animals, Antibodies, Axons, Brain Stem, Cell Compartmentation, Macaca mulatta, Neurons, Rabbits, Alternative Splicing, Receptors, Dopamine D2
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
