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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)


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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]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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]

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 J. Biol. Chem.Home page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 J HeredHome page
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] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. Barajas-Lopez, L. M. Montano, and R. Espinosa-Luna
Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons
Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1238 - G1248.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
P. Borgdorff, D. Fekkes, and G. J. Tangelder
Hypotension Caused by Extracorporeal Circulation: Serotonin From Pump-Activated Platelets Triggers Nitric Oxide Release
Circulation, November 12, 2002; 106(20): 2588 - 2593.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
L.-W. Fu and J. C Longhurst
Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptors
J. Physiol., November 1, 2002; 544(3): 897 - 912.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
R. C. Foehring, J. F. M. van Brederode, G. A. Kinney, and W. J. Spain
Serotonergic Modulation of Supragranular Neurons in Rat Sensorimotor Cortex
J. Neurosci., September 15, 2002; 22(18): 8238 - 8250.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
B. D. Stout, W. P. Clarke, and K. A. Berg
Rapid Desensitization of the Serotonin2C Receptor System: Effector Pathway and Agonist Dependence
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 957 - 962.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
R. Kinkead, O. Belzile, and R. Gulemetova
Serotonergic modulation of respiratory motor output during tadpole development
J Appl Physiol, September 1, 2002; 93(3): 936 - 946.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
H. Hasuo, T. Matsuoka, and T. Akasu
Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus
J. Neurosci., September 1, 2002; 22(17): 7509 - 7517.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
P. C. Moser, O. E. Bergis, S. Jegham, A. Lochead, E. Duconseille, J.-P. Terranova, D. Caille, I. Berque-Bestel, F. Lezoualc'h, R. Fischmeister, et al.
SL65.0155, A Novel 5-Hydroxytryptamine4 Receptor Partial Agonist with Potent Cognition-Enhancing Properties
J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 731 - 741.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
P. Bonaventure, D. Nepomuceno, A. Kwok, W. Chai, X. Langlois, R. Hen, K. Stark, N. Carruthers, and T. W. Lovenberg
Reconsideration of 5-Hydroxytryptamine (5-HT)7 Receptor Distribution Using [3H]5-Carboxamidotryptamine and [3H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT1A Knockout and 5-HT1A/1B Double-Knockout Mice
J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 240 - 248.
[Abstract] [Full Text] [PDF]

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 GutHome page
J Tack and G Sarnelli
Serotonergic modulation of visceral sensation: upper gastrointestinal tract
Gut, July 1, 2002; 51(90001): i77 - 80.
[Abstract] [Full Text]

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 J Biomol ScreenHome page
G. Kaler, M. Otto, A. Okun, and I. Okun
Serotonin Antagonist Profiling on 5HT2A and 5HT2C Receptors by Nonequilibrium Intracellular Calcium Response Using an Automated Flow-Through Fluorescence Analysis System, HT-PS(R)0
J Biomol Screen, June 1, 2002; 7(3): 291 - 301.
[Abstract] [PDF]

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 J. Appl. Physiol.Home page
K. A. Moore, E. J. Oh, and D. Weinreich
5-HT3 receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro
J Appl Physiol, June 1, 2002; 92(6): 2529 - 2534.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
B. Boutrel, C. Monaca, R. Hen, M. Hamon, and J. Adrien
Involvement of 5-HT1A Receptors in Homeostatic and Stress-Induced Adaptive Regulations of Paradoxical Sleep: Studies in 5-HT1A Knock-Out Mice
J. Neurosci., June 1, 2002; 22(11): 4686 - 4692.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
P. Manivet, B. Schneider, J. C. Smith, D.-S. Choi, L. Maroteaux, O. Kellermann, and J.-M. Launay
The Serotonin Binding Site of Human and Murine 5-HT2B Receptors. MOLECULAR MODELING AND SITE-DIRECTED MUTAGENESIS
J. Biol. Chem., May 3, 2002; 277(19): 17170 - 17178.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
H. Lefebvre, D. Cartier, C. Duparc, I. Lihrmann, V. Contesse, C. Delarue, M. Godin, R. Fischmeister, H. Vaudry, and J.-M. Kuhn
Characterization of Serotonin4 Receptors in Adrenocortical Aldosterone-Producing Adenomas: In Vivo and in Vitro Studies
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1211 - 1216.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
S. Boehm and H. Kubista
Fine Tuning of Sympathetic Transmitter Release via Ionotropic and Metabotropic Presynaptic Receptors
Pharmacol. Rev., March 1, 2002; 54(1): 43 - 99.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
A. Laurent, J.-M. Goaillard, O. Cases, C. Lebrand, P. Gaspar, and N. Ropert
Activity-Dependent Presynaptic Effect of Serotonin 1B Receptors on the Somatosensory Thalamocortical Transmission in Neonatal Mice
J. Neurosci., February 1, 2002; 22(3): 886 - 900.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
P. J. Goadsby, R. B. Lipton, and M. D. Ferrari
Migraine -- Current Understanding and Treatment
N. Engl. J. Med., January 24, 2002; 346(4): 257 - 270.
[Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
K. P. Zuideveld, N. Treijtel, H. J. Maas, J. M. Gubbens-Stibbe, L. A. Peletier, P. H. van der Graaf, and M. Danhof
A Competitive Interaction Model Predicts the Effect of WAY-100,635 on the Time Course of R-(+)-8-Hydroxy-2-(di-n-propylamino)tetralin-Induced Hypothermia
J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 330 - 338.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. M. Johnson, J. E. R. Wilkerson, D. R. Henderson, M. R. Wenninger, and G. S. Mitchell
Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro
J Appl Physiol, December 1, 2001; 91(6): 2703 - 2712.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
A. Leonardi, L. Guarneri, E. Poggesi, P. Angelico, C. Velasco, A. Cilia, and R. Testa
N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) Cyclohexanecarboxamide: A Novel Pre- and Postsynaptic 5-Hydroxytryptamine1A Receptor Antagonist Active on the Lower Urinary Tract
J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 1027 - 1037.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
M. Marcoli, C. Rosu, A. Bonfanti, M. Raiteri, and G. Maura
Inhibitory Presynaptic 5-Hydroxytryptamine2A Receptors Regulate Evoked Glutamate Release from Rat Cerebellar Mossy Fibers
J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 1106 - 1111.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
K. A. Berg, B. D. Stout, S. Maayani, and W. P. Clarke
Differences in Rapid Desensitization of 5-Hydroxytryptamine2A and 5-Hydroxytryptamine2C Receptor-Mediated Phospholipase C Activation
J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 593 - 602.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
M. Riad, K. C. Watkins, E. Doucet, M. Hamon, and L. Descarries
Agonist-Induced Internalization of Serotonin-1A Receptors in the Dorsal Raphe Nucleus (Autoreceptors) But Not Hippocampus (Heteroreceptors)
J. Neurosci., November 1, 2001; 21(21): 8378 - 8386.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
Y. Wang and A. G Ramage
The role of central 5-HT1A receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats
J. Physiol., November 1, 2001; 536(3): 753 - 767.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
H. Hashimoto, N. Shintani, K. Tanaka, W. Mori, M. Hirose, T. Matsuda, M. Sakaue, J.-i. Miyazaki, H. Niwa, F. Tashiro, et al.
Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)
PNAS, October 25, 2001; (2001) 231094498.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
Y. Zhang, D. D'Souza, D. K. Raap, F. Garcia, G. Battaglia, N. A. Muma, and L. D. Van de Kar
Characterization of the Functional Heterologous Desensitization of Hypothalamic 5-HT1A Receptors after 5-HT2A Receptor Activation
J. Neurosci., October 15, 2001; 21(20): 7919 - 7927.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
J. F. Lopez-Gimenez, M. Villazon, J. Brea, M. I. Loza, J. M. Palacios, G. Mengod, and M. T. Vilaro
Multiple Conformations of Native and Recombinant Human 5-Hydroxytryptamine2A Receptors Are Labeled by Agonists and Discriminated by Antagonists
Mol. Pharmacol., October 1, 2001; 60(4): 690 - 699.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
T. Suzuki, M. Miura, K.-y. Nishimura, and T. Aosaki
Dopamine-Dependent Synaptic Plasticity in the Striatal Cholinergic Interneurons
J. Neurosci., September 1, 2001; 21(17): 6492 - 6501.
[Abstract] [Full Text] [PDF]


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