MUSCARINIC RECEPTORS IN RAT SYMPATHETIC GANGLIA

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Abstract
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 [Ca2+]o. 3 Mean ED50 values (μm) for depolarization at 25°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’. ED50 values (μm) 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 (K1 0.49 nm) atropine (K1 0.24 nm) methylscopolamine (K1 0.09 nm) lachesine (K1 0.15 nm) and (weakly) by hexamethonium (K1 0.2 mm). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 times 105 m−1s−1. 5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission. 6 Muscarine (1 to 100 μm) initially reduced, then increased, the rate of 86Rb+-efflux from isolated ganglia at both 6 and 120 mm [K+]o. These effects were reduced by 1 μm 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 ED50 values (μm) 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 K1 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 ED50 and antagonist K1 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.