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Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit
Author(s) -
Maclagan Jennifer,
Faulkner David
Publication year - 1989
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.1476-5381.1989.tb11979.x
Subject(s) - pirenzepine , muscarinic acetylcholine receptor , bronchoconstriction , endocrinology , medicine , atropine , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m2 , acetylcholine , chemistry , bradycardia , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m4 , gallamine triethiodide , receptor , heart rate , blood pressure , asthma
1 The effect of muscarinic antagonists considered to be selective for M 1 receptors (pirenzepine) and for M 2 receptors (gallamine) were studied on bronchoconstriction and bradycardia elicited by stimulation of the vagal nerves and by i.v. acetylcholine (ACh) in anaesthetized rabbits. 2 Pirenzepine was equipotent as an antagonist of ACh‐induced responses at postjunctional muscarinic receptors in the heart, lung and blood vessels, whereas gallamine was at least ten times less potent at pulmonary and vascular muscarinic receptors. Thus, gallamine never caused complete inhibition of bronchoconstrictor or hypotensive responses to i.v. ACh, whereas doses of pirenzepine in excess of 1 μmol kg −1 abolished all muscarinic responses. 3 In the lung, both antagonists inhibited bronchoconstriction caused by vagal stimulation and ACh‐induced bronchoconstriction to the same extent (pirenzepine, mean ED 50 65 ± 22 and 130 ± 28 nmol kg −1 respectively; gallamine, ED 50 > 10,000 nmol kg −1 for both responses). Enhancement of vagally‐induced bronchoconstriction was never observed. 4 In the heart, however, both pirenzepine and gallamine were ten times less potent as antagonists of vagally‐induced bradycardia than of ACh‐induced bradycardia. This differential blockade was unaltered by propranolol (1 mg kg −1 ) pretreatment. 5 It is concluded that there is no evidence for M 1 or M 2 muscarinic receptors in the pulmonary innervation of the rabbit and the potency of the antagonists in abolishing vagally‐induced bronchoconstriction was consistent with blockade of M 3 muscarinic receptors on airway smooth muscle. 6 The results suggest that M 2 muscarinic receptors may exert an inhibitory effect on transmission in the parasympathetic nerves innervating the heart in the rabbit. Blockade of such neuronal receptors would increase transmitter output to the atrial cells and explain the low potency of both antagonists in abolishing vagally‐induced bradycardia in the rabbit.