Mttsmrittic~ re~~/~~~ ru~ jtte M2 a& M3 receptor stt~~~~ pt~ s RYE~~ e~~ resse~ itt nmtty types of sfttoofit tttttsfle ittcltrdiitg gnstyoititesW7l sttrootlf trttrsc~ e, ttrittnry blndder attd mtscthr nrtd ttirwmf bsstre. Activntiort of M3 receptors, air? die G yroteirt G,,, results irt ittcrenseti pol~~ yltosyhoirtosijidc hlpirolt~ sis, r&me of Cn’+ iotts# rout the snrcoplastttic reticttlttrrt mtd co~ tseqtrerrily cnkics co&&on. Qtt~ tttit~~ iott of flte relntioe e. ryressiott of Mz~ ttd M3 rkeytoys Itns~ lt~~ wt tltst the~ ro?? ortjoit of. &i? receptors oftett~ re~~ trtiftff~ es over the M_% receptor~ o~ ttl~ fiott by 4: I or tttcwr. Alt~ to~~ g~ t if is cst~~ lis~ ze~ fltnt Mz receptors yyefeyetitinll!~ link, vii~ n pertrrssis-tolitr-scrlsitiz, e G rrotrirr G,, to inlriDitiotl of~ der~!~ lntr c@~ sc nctiait! j, relrttizd~/Iiftlc is ktt07~ tt cottccyttittg the phpiolppicnl role of the M1 receytor poplrlniiotl. ltr this rcvictu, Richard Eglen and colleagues disorss recettt htn cottcerrrittg the yossiblc role (s) of ttlffscnrittic receptor stfbtypes itt sittootit ttttiscle atrd~~~ r~ ise tfte pltnrttrncofogjcni tttet~ tu~ s for~ isse~ tjttg the~~ f~ trt~~~ t of ffftfsf~ rj? tir receptor stt~~~/~ e5 itt tissttes coexpressitt~ tttu~~ i~~ e receptors.

Muscarinic acetylcholine receptors exist as multiple subtypes, encoded by distinct but homologous genes. Structural and pharmacological criteria (Box 1) have suggested the existence of at least four subtypes, denoted M,, Mz, MS and MJ (Ref. l), whilst a rifth subtype, predicted from the cloning of a fifth gene, awaits a pharmacological equivalent’. Pharmaceutical research into therapeutic agents selective for muscarinic receptor subtypes has recently centred on a search for selective MI receptor agonists for the treatment of cognitive disorders. Reia~ ively little emphasis