MUSCARINIC RECEPTORS IN RAT SYMPATHETIC GANGLIA

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.