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MUSCARINIC RECEPTORS IN RAT SYMPATHETIC GANGLIA
Author(s) -
BROWN D.A.,
FATHERAZI S.,
GARTHWAITE J.,
WHITE R.D.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb09777.x
Subject(s) - muscarine , oxotremorine , hexamethonium , muscarinic acetylcholine receptor , pilocarpine , chemistry , endocrinology , depolarization , medicine , methoctramine , atropine , muscarinic acetylcholine receptor m2 , acetylcholine , reversal potential , neuroscience , receptor , biology , biochemistry , patch clamp , epilepsy
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 (μ m ) 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’. ED 50 values (μ m ) for choline esters (measured in the presence of 2.5 m m hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78. 4 Responses to muscarine were antagonized by hyoscine ( K 1 0.49 n m ) atropine ( K 1 0.24 n m ) methylscopolamine ( K 1 0.09 n m ) lachesine ( K 1 0.15 n m ) and (weakly) by hexamethonium ( K 1 0.2 m m ). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 times 10 5 m −1 s −1 . 5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission. 6 Muscarine (1 to 100 μ m ) initially reduced, then increased, the rate of 86 Rb + ‐efflux from isolated ganglia at both 6 and 120 m m [K + ] o . These effects were reduced by 1 μ m 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 (μ m ) 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 1 values (n m ) 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 1 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.