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Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse
Author(s) -
Menozzi A.,
Pozzoli C.,
Poli E.,
Delvescovo B.,
Serventi P.,
Bertini S.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12108
Subject(s) - muscarinic acetylcholine receptor , atropine , methoctramine , bronchoconstriction , muscarinic acetylcholine receptor m2 , muscarinic antagonist , chemistry , muscarinic acetylcholine receptor m1 , antagonist , stimulation , receptor , endocrinology , acetylcholine , medicine , pharmacology , muscarinic acetylcholine receptor m3 , asthma
We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 ( M 1 ), 2 ( M 2 ), 3 ( M 3 ) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation ( EFS ) or by exogenous AC h in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration‐dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M 1 / M 3 or M 2 / M 3 receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous AC h were competitively antagonized only by atropine (p A 2 = 9.01 ± 0.05). M 3 selective antagonist, up to 10 −6 m , caused a moderate concentration‐dependent rightward shift of AC h curve (p A 2 = 7.96 ± 0.10). These data show that M 3 muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M 1 and M 2 receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M 1 and M 3 receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects.