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Evidence for inhibition of sympathetic neurotransmission by endogenously released acetylcholine in the guinea‐pig trachea
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.tb12512.x
Subject(s) - trachealis muscle , physostigmine , acetylcholine , medicine , endocrinology , vagus nerve , stimulation , cholinergic , atropine , chemistry , potassium channel , charybdotoxin
1 Interactions between pulmonary cholinergic and noradrenergic nerves were studied in the innervated tracheal tube preparation isolated from guinea‐pigs anaesthetized with urethane. Relaxations of the trachealis smooth muscle in response to postganglionic stimulation of the sympathetic nerve were recorded as decreases in the intraluminal pressure of the tracheal tube after the pressure had been raised with the stable thromboxane‐mimetic, U46619. In contrast, contractions following preganglionic stimulation of the vagal nerve trunk were recorded as increases in intraluminal pressure. 2 In approximately half of the preparations studied, concurrent stimulation of the vagal nerve trunk inhibited relaxation responses elicited by stimulation of the sympathetic nerves. The vagi were stimulated at parameters which caused no change in intraluminal pressure, excluding the involvement of postjunctional mechanisms. 3 The effect of simultaneous stimulation of the sympathetic nerve trunk was studied on contractile responses evoked by preganglionic stimulation of the vagus nerve. In 80% of the preparations tested the vagal responses were inhibited. This inhibitory effect of sympathetic nerve stimulation was antagonized by propranolol. 4 The potassium channel agonist, cromakalim, endothelins 1 and 3 and the neuropeptides, vasoactive intestinal peptide, neurokinin A and substance P, did not significantly modulate sympathetic nerve‐induced relaxations. 5 The anticholinesterase drug, physostigmine, induced a concentration‐dependent increase in the intraluminal pressure of the tracheal tube and potentiated the postjunctional action of exogenously applied acetylcholine to contract the guinea‐pig trachealis muscle. In the presence of higher concentrations of physostigmine both vagally‐induced contractions and sympathetic nerve‐induced relaxations were reduced. Atropine blocked both the inhibitory effect of physostigmine on sympathetic relaxations and its postjunctional contractile action on the trachealis smooth muscle. 6 It is concluded that, in the guinea‐pig trachea, acetylcholine released endogenously from pulmonary parasympathetic nerves, either by anticholinesterase drugs or in response to nerve stimulation, can inhibit transmission in the adjacent sympathetic nerves via activation of prejunctional muscarinic heteroreceptors, probably of the M 3 subtype.