The interaction of selective and non-selective antagonists with pre- and postjunctional muscarinic receptor subtypes in the guinea pig trachea

European Journal of Pharmacology
R E ten BergeJ Zaagsma


Muscarinic receptor antagonists were used to study prejunctional M2 and postjunctional M3 receptors in the isolated guinea pig trachea. The effects of four M2-selective muscarinic receptor antagonists (gallamine, methoctramine, AQ-RA 741 and AF-DX 116) were studied on twitch contractions, elicited by electrical field stimulation, of tracheal ring preparations. M1-selective (pirenzepine, (+)- and (-)-telenzepine), M3-selective (4-DAMP-methobromide and UH-AH 371) and non-selective (atropine and ipratropium) muscarinic receptor antagonists were also used. The clear potentiation of the twitch contractions and the subsequent strong inhibition observed with M2-selective antagonists demonstrate antagonism at prejunctional M2 and postjunctional M3 muscarinic receptors, respectively. The maximal potentiation correlated well with the M2/M3-selectivity known from binding experiments: gallamine > methoctramine > AQ-RA 741 > AF-DX 116. Strong correlations were also found between the pEC20 values for potentiation of the twitch response and the pKi values for bovine cardiac M2 muscarinic receptors and between the pIC50 values for inhibition of the twitch response and the pA2 values for M3 muscarinic receptors as determined on non-stimulated m...Continue Reading


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