Muscarinic receptors in rat sympathetic ganglia.
1 Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic-receptor agonists were recorded by an extracellular ;air-gap' method.2 Muscarinic agonists produced a delayed low-amplitude ganglion depolarization, frequently preceded by a hyperpolarization. Potentials were enhanced by reducing [K(+)](o) or [Ca(2+)](o).3 Mean ED(50) values (muM) for depolarization at 25 degrees C were: oxotremorine 0.004, methylfurmethide 0.11, (+/-)-muscarine 0.24, furmethide 1.56, pilocarpine 4.81 and AHR-602 (N-benzylpyrrolidylacetate methobromide) 10.8. Responses produced by oxotremorine, pilocarpine and AHR-602 showed some characteristics of ;partial agonism'. ED(50) values (muM) for choline esters (measured in the presence of 2.5 mM hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78.4 Responses to muscarine were antagonized by hyoscine (K(I) 0.49 nM) atropine (K(I) 0.24 nM) methylscopolamine (K(I) 0.09 nM) lachesine (K(I) 0.15 nM) and (weakly) by hexamethonium (K(I) 0.2 mM). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 x 10(5) M(-1)S(-1).5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission.6 Muscarine (1 to 100 muM) initially reduced, then increased, the rate of (86)Rb(+)-efflux from isolated ganglia at both 6 and 120 mM [K(+)](o). These effects were reduced by 1 muM hyoscine.7 No consistent change in the amounts of cyclic 3',5'-guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.8 Mean against ED(50) values (muM) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (+/-)-muscarine 0.48, pilocarpine 7.8 and AHR-602 9.9. Mean antagonist K(I) values (nM) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27.9 It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED(50) and antagonist K(I) values, and that the major difference between them lies in the greater ;efficacy' of certain agonists (pilocarpine, AHR-602 and McN-A-343) on the ganglion.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012413:Rubidium / Q000378:metabolism
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D009116:Muscarine; D006152:Cyclic GMP; D012413:Rubidium; D002118:Calcium