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Evidence for prejunctional inhibitory muscarinic receptors on sympathetic nerves innervating guinea‐pig trachealis muscle
Author(s) -
Pendry Yvonne D.,
Maclagan Jennifer
Publication year - 1991
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.1476-5381.1991.tb12318.x
Subject(s) - trachealis muscle , muscarinic acetylcholine receptor , acetylcholine , endocrinology , medicine , chemistry , pilocarpine , gallamine triethiodide , pirenzepine , muscarinic acetylcholine receptor m3 , methoctramine , biology , receptor , potassium channel , neuroscience , charybdotoxin , epilepsy
1 Relaxation responses induced by stimulation of the postganglionic sympathetic nerve trunk were studied in the isolated, fluid‐filled, innervated tracheal tube preparation of the guinea‐pig. 2 The thromboxane‐mimetic U46619, prostaglandin F 2α and histamine each caused concentration‐dependent increases in the intraluminal pressure (ILP) of the fluid‐filled tracheal tube, reflecting contraction of the trachealis muscle. Sympathetic nerve stimulation in the presence of the spasmogens caused relaxations which increased with increasing ILP. Relaxant responses evoked in the presence of these three spasmogens were comparable at any given ILP. 3 Muscarinic agonists caused concentration‐dependent increases in ILP, pilocarpine being more potent than acetylcholine. Sympathetic nerve‐induced relaxations were reduced in the presence of pilocarpine and acetylcholine when compared to those obtained at the same ILP in the presence of U46619. This inhibitory effect of muscarinic agonists on sympathetic nerve‐induced responses was concentration‐dependent. 4 Exogenously applied noradrenaline opposed the contractile effect of U46619 and acetylcholine to a similar extent, indicating that a comparable degree of postjunctional functional antagonism exists between the sympathetic neurotransmitter noradrenaline and both spasmogens. 5 The selective M 2 muscarinic antagonists, gallamine and methoctramine, altered neither the postjunctional contractile action of acetylcholine nor its inhibitory effect on sympathetic nerve‐induced relaxations. In addition, the inhibitory effect of acetylcholine was not modified by concentrations of pirenzepine known to block M 1 muscarinic receptors. 6 The postjunctional contractile action of acetylcholine and its inhibitory effect on sympathetic neurotransmission were antagonized by atropine, by the M 3 muscarinic antagonist hexahydrosiladiphenidol and by higher concentrations of pirenzepine. 7 These results suggest that in the guinea‐pig trachea, muscarinic cholinoreceptor agonists inhibit sympathetic neurotransmission via activation of muscarinic receptors located on the sympathetic nerve endings. These inhibitory prejunctional muscarinic heteroreceptors are of the M 3 subtype.