• ↵9-a These abbreviations are proposed to establish and maintain consistency with existing internationally authoritative nomenclature databases (e.g., GDB, MEDLINE). Alternative abbreviations to denote the species when using trivial receptor names have been published by NC-IUPHAR, and these are still appropriate for use in textual discussion referring to trivial names (see Vanhoutte et al., 1996).

• ↵10-a No code for trinucleotide repeats is recommended; these can be described in the text associated with the relevant RC.

• ↵2-a Each main receptor structure class is subdivided as outlined in Tables 3-6. If the subclass is not known definitively, the main class only will be identified as 1.0, 2.0, etc. These classes are provisional, and additional classes and subclasses may need to be added as knowledge increases. Literature references on receptors in many of the subclasses listed can be found in The IUPHAR Compendium of Receptor Characterization and Classification.

(ion-channel receptors)

• ↵3-a It should be noted that subclass 1.3 will contain at least two protein superfamilies, which do not share any sequence homology. One comprises the cyclic nucleotide receptors and the second comprises the IP₃ and the ryanodine receptors.

• ↵3-b It is recognized that the definition of subclasses 1.6, 1.7, and 1.8 may require modification as knowledge of them increases, but they serve to illustrate the full potential of the proposed coding system.

• ↵3-c Several K_ATP channel subtypes are known in different tissues, differing greatly in their response to inhibitory sulfonyl ureas (SUR) and to channel-opening drugs such as diazoxide. Their structures, as known so far by DNA cloning, contain two unrelated subunits, an inward rectifier K⁺ channel protein (from the Kir.6 series) and a sulfonylurea- and nucleotide-binding protein (SUR); a family of SURs produce variations in the K_ATPpharmacology (Inagaki et al., 1996). Therefore,K_ATP channel subunits will be numbered in two series; for the KIR (6.1), etc., subunits as 1.6.KIR.61.S [or 62.S, etc.] and for the SUR1, etc., subunits 1.6.SUR.01.S [or 02.S etc.], and the entire K_ATP channel as 1.6.NUCT.01.M [or 02.M, etc.] when definitive evidence for the subunit composition is known.

• ↵3-d Although genes for types 1.7 and 1.8 have each been cloned, expressed, and shown to correspond to channels seen in native tissues (Baukrowvitz et al., 1994; Fairman et al., 1995), the precise relationship of the ion channel to the transporter in these types is at present unclear. Transporters are not necessarily ligand-gated channels: however, in addition to the case of glutamate transporters, transporters of serotonin (5-HT) and of dopamine incorporate, respectively, a 5-HT-gated channel (Galli et al., 1997) or a dopamine-gated channel (Sonders et al., 1997), and this principle may hold also for norepinephrine and γ-aminobutyric acid transporters (Sonders and Amara, 1996).

(G protein-coupled receptors)

•  The subclasses shown have been classified according to their protein sequences so that within a subclass all receptor types share significant similarity (i.e., ≥20% sequence identity) throughout the predicted hydrophobic transmembrane domains (Kolakowski, 1994; see also the G protein-Coupled Receptor Database at www.gcrdb.ulthscsa.edu).

• ↵4-a From the strict structural viewpoint, Class 2.1 is not homogeneous. All its members comprise a seven-transmembrane amino acid chain, but in a very few, the active receptor is formed from this by a proteolytic cleavage. The first described was the thrombin receptor (2.1.THR), in which the agonist thrombin specifically cleaves the receptor chain to liberate a new N-terminal segment and activate the receptor (Vu et al., 1991). Others are the thyrotropin receptor (2.1.TSH), where a peptidase produces two extracellular chains (Misrahi et al., 1994), and other protease-activated receptors where the natural agonist is an unidentified trypsin-like protease (Nystedt et al., 1995; Ishihara et al., 1997).

(enzyme-associated single transmembrane domain receptors)

(transcriptional regulator receptors)

• Nuclear receptors constitute a distinctive class which has great therapeutic relevance but recently has been overlooked somewhat by pharmacologists. With the discovery of multiple orphan nuclear receptors and hence of other potential structural subclasses (seeKastner et al., 1995; Mangelsdorf et al., 1995; Laudet et al., 1998), we suggest that effort should be applied to further subclassification of this class on the basis of the integrated pharmacological approach proposed here.

• ↵7-a This list is not exhaustive but represents receptor families for which classifications are well developed and a few illustrations of newer receptor families that are not well classified.