Receptor subtypes,multiplicity molecular cloning

The opioid peptides vary in their binding affinities for the multiple opioid receptor types. Leu- and Met-enkephalin have a higher affinity for 5-receptors than for the other opioid receptor types (68), whereas the dynorphin peptides have a higher affinity for K-sites (69). P-Endorphin binds with equal affinity to both p- and 5-receptors, but binds with lower affinity to K-sites (70). The existence of a P-endorphin-selective receptor, the S-receptor, has been postulated whether this site is actually a separate P-endorphin-selective receptor or is a subtype of a classical opioid receptor is a matter of controversy (71,72). The existence of opioid receptor subtypes in general is quite controversial although there is some evidence for subtypes of p- (73), 5-(74), and K-receptors (72,75), confirmation of which may be obtained by future molecular cloning studies. 

Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

The identification of multiple muscarinic receptor subtypes has stimulated the search for ligands with selectivity for a given receptor subtype [34-36]. Five different subt rpes (mi-ms) have been identified so far by molecular cloning. Muscarinic receptors that have been characterized pharmacologically and classified as M1-M4, appear to correspond to cloned m]-m4 receptors. At present, little information is available about the nature and the cellular location of the m5 subtype. 

Molecular genetic techniques have confirmed the existence of multiple subtypes of p-adrenoceptors. Pi-Receptors and Pj-receptors have been cloned, and recent molecular biological evidence indicates the existence of at least one additional p-receptor sub-type, called the p3-receptor. It is suggested that the P3-receptor may mediate some of the metabolic effects of catecholamines, although no available p-blocker has been shown to rely on Pa-receptor antagonism for its therapeutic effectiveness. 

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