Pharmacological Reviews, Vol 46, 157-203, Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

International Union of Pharmacology classification of receptors for 5- hydroxytryptamine (Serotonin)

D Hoyer, DE Clarke, JR Fozard, PR Hartig, GR Martin, EJ Mylecharane, PR Saxena and PP Humphrey
Sandoz Pharma Limited, Basel, Switzerland.

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics. This derives from two main research approaches, operational pharmacology, using selective ligands (both agonists and antagonists), and, more recently, molecular biology. Although the scientific community continues to deliberate about the hierarchy of criteria for neurotransmitter receptor characterisation, there seems good agreement between the two approaches regarding 5-HT receptor classification. In addition, the information regarding transduction mechanisms and second messengers is also entirely consistent. Thus, on the basis of these essential criteria for receptor characterisation and classification, there are at least three main groups or classes of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only operationally but also structurally distinct, with each receptor group having its own distinct transducing system. The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known. Although those 5-HT receptors that have been fully characterised and classified to date (and, hence, named with confidence) would seem to mediate the majority of the actions of 5-HT throughout the mammalian body, not all receptors for 5-HT are fully encompassed within our scheme of classification. These apparent anomalies must be recognised and need further study. They may or may not represent new groups of 5-HT receptor or subtypes of already known groups of 5-HT receptor. Even though the cDNAs for the 5-ht1E, 5-ht1F, 5-ht5, 5-ht6, and 5-ht7 receptors have been cloned and their amino acid sequence defined, more data are necessary concerning their operational and transductional characteristics before one can be confident of the suitability of their appellations. Therefore, it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				L. M. Hurley, J. A. Tracy, and A. Bohorquez Serotonin 1B Receptor Modulates Frequency Response Curves and Spectral Integration in the Inferior Colliculus by Reducing GABAergic Inhibition J Neurophysiol, September 1, 2008; 100(3): 1656 - 1667. [Abstract] [Full Text] [PDF]

				D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]

				C. Fligny, Y. Fromes, P. Bonnin, M. Darmon, E. Bayard, J.-M. Launay, F. Cote, J. Mallet, and G. Vodjdani Maternal serotonin influences cardiac function in adult offspring FASEB J, July 1, 2008; 22(7): 2340 - 2349. [Abstract] [Full Text] [PDF]

				Q. Liu and M. T. T. Wong-Riley Postnatal changes in the expression of serotonin 2A receptors in various brain stem nuclei of the rat J Appl Physiol, June 1, 2008; 104(6): 1801 - 1808. [Abstract] [Full Text] [PDF]

				K. B. Fink and M. Gothert 5-HT Receptor Regulation of Neurotransmitter Release Pharmacol. Rev., December 1, 2007; 59(4): 360 - 417. [Abstract] [Full Text] [PDF]

				A. E. Linder, W. Ni, J. L. Diaz, T. Szasz, R. Burnett, and S. W. Watts Serotonin (5-HT) in Veins: Not All in Vain J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 415 - 421. [Abstract] [Full Text] [PDF]

				J. Shi, K. J. Damjanoska, R. K. Singh, G. A. Carrasco, F. Garcia, A. J. Grippo, M. Landry, N. R. Sullivan, G. Battaglia, and N. A. Muma Agonist Induced-Phosphorylation of G{alpha}11 Protein Reduces Coupling to 5-HT2A Receptors J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 248 - 256. [Abstract] [Full Text] [PDF]

				A. Papageorgiou and C. Denef Stimulation of Growth Hormone Release by 5-Hydroxytryptamine (5-HT) in Cultured Rat Anterior Pituitary Cell Aggregates: Evidence for Mediation by 5-HT2B, 5-HT7, 5-HT1B, and Ketanserin-Sensitive Receptors Endocrinology, September 1, 2007; 148(9): 4509 - 4522. [Abstract] [Full Text] [PDF]

				P. Svenningsson, E. T. Tzavara, H. Qi, R. Carruthers, J. M. Witkin, G. G. Nomikos, and P. Greengard Biochemical and Behavioral Evidence for Antidepressant-Like Effects of 5-HT6 Receptor Stimulation J. Neurosci., April 11, 2007; 27(15): 4201 - 4209. [Abstract] [Full Text] [PDF]

				A. Papageorgiou and C. Denef Estradiol Induces Expression of 5-Hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 Receptor Messenger Ribonucleic Acid in Rat Anterior Pituitary Cell Aggregates and Allows Prolactin Release via the 5-HT4 Receptor Endocrinology, March 1, 2007; 148(3): 1384 - 1395. [Abstract] [Full Text] [PDF]

				H.-M. Yun, S. Kim, H.-J. Kim, E. Kostenis, J. I. Kim, J. Y. Seong, J.-H. Baik, and H. Rhim The Novel Cellular Mechanism of Human 5-HT6 Receptor through an Interaction with Fyn J. Biol. Chem., February 23, 2007; 282(8): 5496 - 5505. [Abstract] [Full Text] [PDF]

				J. D. Urban, W. P. Clarke, M. von Zastrow, D. E. Nichols, B. Kobilka, H. Weinstein, J. A. Javitch, B. L. Roth, A. Christopoulos, P. M. Sexton, et al. Functional Selectivity and Classical Concepts of Quantitative Pharmacology J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 1 - 13. [Abstract] [Full Text] [PDF]

				L. M. Hurley Different Serotonin Receptor Agonists Have Distinct Effects on Sound-Evoked Responses in Inferior Colliculus J Neurophysiol, November 1, 2006; 96(5): 2177 - 2188. [Abstract] [Full Text] [PDF]

				N. A. Sharif, C. R. Kelly, and M. McLaughlin Human Trabecular Meshwork Cells Express Functional Serotonin-2A (5HT2A) Receptors: Role in IOP Reduction. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4001 - 4010. [Abstract] [Full Text] [PDF]

				C. R. Kelly and N. A. Sharif Pharmacological Evidence for a Functional Serotonin-2B Receptor in a Human Uterine Smooth Muscle Cell Line J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1254 - 1261. [Abstract] [Full Text] [PDF]

				B. Dumitriu, J. E. Cohen, Q. Wan, A. M. Negroiu, and T. W. Abrams Serotonin Receptor Antagonists Discriminate Between PKA- and PKC-Mediated Plasticity in Aplysia Sensory Neurons J Neurophysiol, April 1, 2006; 95(4): 2713 - 2720. [Abstract] [Full Text] [PDF]

				N. Madjid, E. E. Tottie, M. Luttgen, B. Meister, J. Sandin, A. Kuzmin, O. Stiedl, and S. O. Ogren 5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 581 - 591. [Abstract] [Full Text] [PDF]

				J. R. Grider Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G319 - G327. [Abstract] [Full Text] [PDF]

				G. D'Agostino, A. M. Condino, P. Gallinari, G. P. Franceschetti, and M. Tonini Characterization of Prejunctional Serotonin Receptors Modulating [3H]Acetylcholine Release in the Human Detrusor J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 129 - 135. [Abstract] [Full Text] [PDF]

				L. Xue, G. R. Locke, M. Camilleri, J. A. J. Schuurkes, A. Meulemans, B. J. Coulie, J. H. Szurszewski, and G. Farrugia Effect of modulation of serotonergic, cholinergic, and nitrergic pathways on murine fundic size and compliance measured by ultrasonomicrometry Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G74 - G82. [Abstract] [Full Text] [PDF]

				K. W. Andressen, J. H. Norum, F. O. Levy, and K. A. Krobert Activation of Adenylyl Cyclase by Endogenous Gs-Coupled Receptors in Human Embryonic Kidney 293 Cells Is Attenuated by 5-HT7 Receptor Expression Mol. Pharmacol., January 1, 2006; 69(1): 207 - 215. [Abstract] [Full Text] [PDF]

				D. Cartier, S. Jegou, F. Parmentier, I. Lihrmann, E. Louiset, J.-M. Kuhn, C. Bastard, P.-F. Plouin, M. Godin, H. Vaudry, et al. Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenomas Eur. J. Endocrinol., December 1, 2005; 153(6): 939 - 947. [Abstract] [Full Text] [PDF]

				K. J. Miller SEROTONIN 5-HT2C RECEPTOR AGONISTS: POTENTIAL FOR THE TREATMENT OF OBESITY Mol. Interv., October 1, 2005; 5(5): 282 - 291. [Abstract] [Full Text] [PDF]

				N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]

				J. H. Turner and J. R. Raymond Interaction of Calmodulin with the Serotonin 5-Hydroxytryptamine2A Receptor: A PUTATIVE REGULATOR OF G PROTEIN COUPLING AND RECEPTOR PHOSPHORYLATION BY PROTEIN KINASE C J. Biol. Chem., September 2, 2005; 280(35): 30741 - 30750. [Abstract] [Full Text] [PDF]

				N. A. Otmakhova, J. Lewey, B. Asrican, and J. E. Lisman Inhibition of Perforant Path Input to the CA1 Region by Serotonin and Noradrenaline J Neurophysiol, August 1, 2005; 94(2): 1413 - 1422. [Abstract] [Full Text] [PDF]

				V. Contesse, Y. Reznik, E. Louiset, C. Duparc, D. Cartier, F. Sicard, A. Laquerriere, F. Parmentier, J.-M. Kuhn, H. Vaudry, et al. Abnormal Sensitivity of Cortisol-Producing Adrenocortical Adenomas to Serotonin: In Vivo and in Vitro Studies J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2843 - 2850. [Abstract] [Full Text] [PDF]

				T. Durk, E. Panther, T. Muller, S. Sorichter, D. Ferrari, C. Pizzirani, F. Di Virgilio, D. Myrtek, J. Norgauer, and M. Idzko 5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes Int. Immunol., May 1, 2005; 17(5): 599 - 606. [Abstract] [Full Text] [PDF]

				S. Saksena, R. K. Gill, S. Tyagi, W. A. Alrefai, Z. Sarwar, K. Ramaswamy, and P. K. Dudeja Involvement of c-Src and Protein Kinase C{delta} in the Inhibition of Cl-/OH- Exchange Activity in Caco-2 Cells by Serotonin J. Biol. Chem., March 25, 2005; 280(12): 11859 - 11868. [Abstract] [Full Text] [PDF]

				E. W. Boyer and M. Shannon The Serotonin Syndrome N. Engl. J. Med., March 17, 2005; 352(11): 1112 - 1120. [Full Text] [PDF]

				Z. Xiang, L. Wang, and S. T. Kitai Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes J Neurophysiol, March 1, 2005; 93(3): 1145 - 1157. [Abstract] [Full Text] [PDF]

				E. Qvigstad, T. Brattelid, I. Sjaastad, K. W. Andressen, K. A. Krobert, J. A. Birkeland, O. M. Sejersted, A. J. Kaumann, T. Skomedal, J.-B. Osnes, et al. Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to serotonin in heart failure Cardiovasc Res, March 1, 2005; 65(4): 869 - 878. [Abstract] [Full Text] [PDF]

				S. Mouillet-Richard, M. Pietri, B. Schneider, C. Vidal, V. Mutel, J.-M. Launay, and O. Kellermann Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein J. Biol. Chem., February 11, 2005; 280(6): 4592 - 4601. [Abstract] [Full Text] [PDF]

				G. F. Elphick, W. Querbes, J. A. Jordan, G. V. Gee, S. Eash, K. Manley, A. Dugan, M. Stanifer, A. Bhatnagar, W. K. Kroeze, et al. The Human Polyomavirus, JCV, Uses Serotonin Receptors to Infect Cells Science, November 19, 2004; 306(5700): 1380 - 1383. [Abstract] [Full Text] [PDF]

				T. Tanimoto, M. Takeda, T. Nishikawa, and S. Matsumoto The Role of 5-Hydroxytryptamine3 Receptors in the Vagal Afferent Activation-Induced Inhibition of the First Cervical Dorsal Horn Spinal Neurons Projected from Tooth Pulp in the Rat J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 803 - 810. [Abstract] [Full Text] [PDF]

				L. A. Hazelwood and E. Sanders-Bush His452Tyr Polymorphism in the Human 5-HT2A Receptor Destabilizes the Signaling Conformation Mol. Pharmacol., November 1, 2004; 66(5): 1293 - 1300. [Abstract] [Full Text] [PDF]

				F De Ponti Pharmacology of serotonin: what a clinician should know Gut, October 1, 2004; 53(10): 1520 - 1535. [Full Text] [PDF]

				B. Gu, K. J. Olejar, J. P. Reiter, K. B. Thor, and P. C. Dolber Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 1266 - 1272. [Abstract] [Full Text] [PDF]

				D. J. Welsh, M. Harnett, M. MacLean, and A. J. Peacock Proliferation and Signaling in Fibroblasts: Role of 5-Hydroxytryptamine2A Receptor and Transporter Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 252 - 259. [Abstract] [Full Text] [PDF]

				C. P. Bengtson, D. J. Lee, and P. B. Osborne Opposing Electrophysiological Actions of 5-HT on Noncholinergic and Cholinergic Neurons in the Rat Ventral Pallidum In Vitro J Neurophysiol, July 1, 2004; 92(1): 433 - 443. [Abstract] [Full Text] [PDF]

				Y. Zhang, T. S. Gray, D. N. D'Souza, G. A. Carrasco, K. J. Damjanoska, B. Dudas, F. Garcia, G. M. Zainelli, N. R. Sullivan Hanley, G. Battaglia, et al. Desensitization of 5-HT1A Receptors by 5-HT2A Receptors in Neuroendocrine Neurons in Vivo J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 59 - 66. [Abstract] [Full Text] [PDF]

				M. D. McDonald and P. J. Walsh Dogmas and controversies in the handling of nitrogenous wastes: 5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish, Opsanus beta J. Exp. Biol., May 15, 2004; 207(12): 2003 - 2010. [Abstract] [Full Text] [PDF]

				M. Idzko, E. Panther, C. Stratz, T. Muller, H. Bayer, G. Zissel, T. Durk, S. Sorichter, F. Di Virgilio, M. Geissler, et al. The Serotoninergic Receptors of Human Dendritic Cells: Identification and Coupling to Cytokine Release J. Immunol., May 15, 2004; 172(10): 6011 - 6019. [Abstract] [Full Text] [PDF]

				L. G. Costa, L. Steardo, and V. Cuomo Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects Pharmacol. Rev., March 1, 2004; 56(1): 103 - 147. [Abstract] [Full Text] [PDF]

				M. McGuire, Y. Zhang, D. P. White, and L. Ling Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R334 - R341. [Abstract] [Full Text] [PDF]

				J. Y. Crider, G. W. Williams, C. D. Drace, P. Katoli, M. Senchyna, and N. A. Sharif Pharmacological Characterization of a Serotonin Receptor (5-HT7) Stimulating cAMP Production in Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4837 - 4844. [Abstract] [Full Text] [PDF]

				C. Waeber and M. A. Moskowitz Therapeutic implications of central and peripheral neurologic mechanisms in migraine Neurology, October 28, 2003; 61(90084): S9 - 20. [Full Text]

				E. Sanders-Bush, H. Fentress, and L. Hazelwood Serotonin 5-HT2 Receptors: Molecular and Genomic Diversity Mol. Interv., September 1, 2003; 3(6): 319 - 330. [Abstract] [Full Text] [PDF]

				A. Meneses A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory Learn. Mem., September 1, 2003; 10(5): 363 - 372. [Abstract] [Full Text] [PDF]

				D. Barbas, L. DesGroseillers, V. F. Castellucci, T. J. Carew, and S. Marinesco Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes Learn. Mem., September 1, 2003; 10(5): 373 - 386. [Abstract] [Full Text] [PDF]

				C. Cao, J. H. Han, S. Z. Kim, K. W. Cho, and S. H. Kim Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes Cardiovasc Res, August 1, 2003; 59(2): 360 - 368. [Abstract] [Full Text] [PDF]

				T. Manzke, U. Guenther, E. G. Ponimaskin, M. Haller, M. Dutschmann, S. Schwarzacher, and D. W. Richter 5-HT4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia Science, July 11, 2003; 301(5630): 226 - 229. [Abstract] [Full Text] [PDF]

				F. De Ponti, F. Crema, E. Moro, G. Nardelli, G. Frigo, and A. Crema Role of 5-HT1B/D receptors in canine gastric accommodation: effect of sumatriptan and 5-HT1B/D receptor antagonists Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G96 - G104. [Abstract] [Full Text] [PDF]

				M. Sasaki, H. Obata, S. Saito, and F. Goto Antinociception with Intrathecal {alpha}-Methyl-5-Hydroxytryptamine, a 5-Hydroxytryptamine2A/2C Receptor Agonist, in Two Rat Models of Sustained Pain Anesth. Analg., April 1, 2003; 96(4): 1072 - 1078. [Abstract] [Full Text] [PDF]

				Z. Xiang and D. A. Prince Heterogeneous Actions of Serotonin on Interneurons in Rat Visual Cortex J Neurophysiol, March 1, 2003; 89(3): 1278 - 1287. [Abstract] [Full Text] [PDF]

				J. E. Cohen, C. U. Onyike, V. L. McElroy, A. H. Lin, and T. W. Abrams Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors J Neurophysiol, March 1, 2003; 89(3): 1440 - 1455. [Abstract] [Full Text] [PDF]

				K. E. Scrogin 5-HT1A receptor agonist 8-OH-DPAT acts in the hindbrain to reverse the sympatholytic response to severe hemorrhage Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R782 - R791. [Abstract] [Full Text] [PDF]

				J. H. Norum, K. Hart, and F. O. Levy Ras-dependent ERK Activation by the Human Gs-coupled Serotonin Receptors 5-HT4(b) and 5-HT7(a) J. Biol. Chem., January 24, 2003; 278(5): 3098 - 3104. [Abstract] [Full Text] [PDF]

				D. Cartier, I. Lihrmann, F. Parmentier, C. Bastard, J. Bertherat, P. Caron, J.-M. Kuhn, A. Lacroix, A. Tabarin, J. Young, et al. Overexpression of Serotonin4 Receptors in Cisapride-Responsive Adrenocorticotropin-Independent Bilateral Macronodular Adrenal Hyperplasia Causing Cushing's Syndrome J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 248 - 254. [Abstract] [Full Text] [PDF]

L. van den Berg, S. A. Versteeg, and B. A. van Oost Isolation and Characterization of the Canine Serotonin Receptor 1A Gene (htr1A) J. Hered., January 1, 2003; 94(1): 49 - 56. [Abstract] [Full Text]