5-HT receptors classification

Hoyer D, Martin G (1997) 5-HT receptor classification and nomenclatm-e towards a harmonization with the himian genome. Neuropharmacology 36 419-428 Hynes M, Ye W, Wang K, Stone D, Murone M, Sauvage F, Rosenthal A (2000) The seven-transmembrane receptor smoothened cell-autonomously induces multiple ventral cell types. Nat Neurosci 3 41-46... 

Hoyer D, Martin G. 5-HT receptor classification and nomenclature towards a harmonization with the human genome. Neuropharmacology 1997 36 419-28. 

Serotoninergic System. Figure 1 Graphical representation of the current classification of 5-hydroxytryptamine (5-HT) receptors. Receptor subtypes represented by shaded boxes and lowercase designate receptors that have not been demonstrated to definitively function in native systems. Abbreviations 3-5r cyclic adenosine monophosphate (cAMP) phospholipase C (PLC) negative (-ve) positive (+ve)... 

Hoyer, D. Martin, G. R. (1996). Classification and nomenclature of 5-HT receptors a comment on current issues. Behav. Brain Res. 73, 263-8. 

The biochemistry and pharmacology of 5-HT receptors have been reviewed [74], therapeutic implications presented [75, 76], and functional classification proposed [77], Recently, the neuroanatomy, physiology and pharmacology of 5-HT, receptors have been reviewed [78]. It is evident that major advances have been made since the Gaddum and Picarelli proposal to subdivide 5-HT receptors into D (dibenzyline sensitive) and M (morphine sensitive) types [79]. Subsequently, the D and M receptors have been identified as 5-HT2 and 5-HT, type, respectively. 

The classification of 5-HT-receptors is still an ongoing field of research. 5-HTi, 5-HT2, 5-HT4, 5-HTe and S-HT subtypes belong to the superfamily of G-protein coupled receptors whereas the 5-HT3 subtype is a ligand-gated ion channel. The activation of 5-HTi-receptors induces excitatory or inhibitory effects in the periphery as well as in the central nervous system. There are presynaptic 5-HTi-autoreceptors. 5-HT2-receptors in the periphery are located postsynaptieally, their stimulation induce only excitatory effects. 

P. Leff, G. R. Martin, and J. M. Morse. Differential classification of vascular smooth muscle and endothelial cell 5-HT receptors by use of tryptamine analogues. Br. J. Pharm. 97 321-331 (1987). 

Table 14.2. Classification and Nomenclature for the Various Populations of 5-HT Receptors...

Table 14.2 lists the receptor classification and nomenclatures that have been employed for serotonergic receptors. Other 5-HT orphan receptors that have not yet been cloned include the 5-HTip receptors, which are found only in the gastrointestinal tract. Care should be used when reading the older primary literature, because 5-HT receptor nomenclature has changed so dramatically and often can be confusing and very frustrating to comprehend. 

At the present time, the differentiation of 5-HT receptors into 3 molecular types of receptors appears to be the most relevant classification system (Table 1). A variety of data indicate that multiple other, as yet unidentified, 5-HT receptor subtypes also exist. Further studies are needed to determine whether the 5-HT4 receptor represents yet another major "family" of 5-HT receptors or, since the site is clearly linked to the stimulation of adenylylcyclase, whether it will eventually be classified as a member of the 5-HTs or 5-HT7 "families". The number of such "orphan" receptors is likely to decrease in the years ahead as a result of the rapidly evolving molecular biological data. 

Recently, the molecular cloning of 14 different mammalian receptor suhtypes revealed an unexpected heterogeneity within 5-HT receptors. The latest classification of 5-HT receptors takes in account not only their pharmacological profile and their coupling with second messengers hut also their amino add sequence (see figure 1, 2 and ref [1]). 

Table 4 Tissues in which neurotransmitter release is increased (j) or decreased (j) by presynaptic5-HT receptor activation. Receptor classification (except with superscript a) as by the authors cited. Designation as 5-HTi4ike where no differentiation between 5-HT,A, 5-HTiB, 5-HTid, 5-HTie, and 5-HT,f was made. Designation as 5-HT2-like where no differentiation between 5-HT2A, 5-HT2B and 5-HT2C was made...

A. Classification and Prototypes Ketanserin is a S-HT and alpha-adrenoceptor blocker. Phe-noxybenzamine (an alpha-adrenoceptor blocker) and cyproheptadine (an Hj blocker) are also good 5-HTj blockers. Ondansetron, granisetron, dolasetron, and alosetron are 5-HTj blockers. The ergot alkaloids are partial agonists at 5-HT and other receptors (see below). 

Based on one current classification system, fourteen serotonin receptor subtypes have been described for the peripheral and central actions of 5-HT. A brief summary is provided in Table 18.1 but the reader is referred to the appropriate pharmacological literature for details. Only the 5-HT3 receptor is a ligand-gated ion channel the remaining subfamilies are G-protein coupled receptors. It is also worth noting that the situation is more complicated based on the presence of additional receptors which... 

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