Classification and nomenclature of 5-HT receptors: a comment on current issues

Abstract

Information concerning the structural, operational and transductional characteristics of 5-HT receptors continues to increase at an incredible pace, challenging our efforts to assimilate and organise it in a comprehensive manner. At the time of the Serotonin Satellite meeting in Chicago, the IUPHAR classification of receptors for 5-HT recognised four distinct receptor classes (5-HT₁, 5-HT₂, 5-HT₃ and 5-HT₄), comprising seven fully characterised functional receptor subtypes and four recombinant receptors (5-HT_1Dα, 5-HT_1Dβ, 5-ht_1E and 5-ht_1F). Four additional recombinant receptors (5-ht_1A, 5-ht_5B, 5-ht₆ and 5-ht₇) provide strong evidence for the existence three additional receptor classes. Indeed, results presented largely at the Chicago meeting have confirmed the physiological importance of both 5-ht₆ and 5-ht₇ receptors so that in future schemes, these will be acknowledged as fully characterised receptor classes. It is evident from this brief review that a number of issues remain to be resolved, and more are certain to follow. Some, for example the definition of the term ‘physiologically relevant’, as applied to recombinant receptors, will long continue to attract debate, especially between molecular biologists and pharmacologists. Others, such as the issue of species primacy, are perhaps more fundamental and can be expected to receive the urgent attention of NC-IUPHAR. These issues notwithstanding, the current scheme clearly provides a secure and rational basis for classifying and naming 5-HT receptors. The continued efforts of the SRNC are intended to encourage its further evolution towards the ultimate goal of a unitary classification for neurotransmitter/hormone receptors.