Differential role of M-1 and M-2 receptors in sympathetic ganglia of the pithed normotensive rat in alpha adrenoceptor-mediated vasoconstriction

B Wilffert, D Davidesko, PB Timmermans and PA van Zwieten

In the pithed normotensive rat the adrenoceptors involved in the hypertensive and tachycardic effects of the muscarinic ganglionic stimulants 1,1-dimethyl-4-carboxypiperidine methylester (DMCPM) and (4- m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) were analyzed. The selective alpha-1 adrenoceptor antagonist prazosin, the selective alpha-2 adrenoceptor antagonist rauwolscine, the selective beta-1 adrenoceptor antagonist atenolol and the selective beta-2 adrenoceptor antagonist ICI 118,551 were used as tools for the identification of the adrenoceptors. DMCPM elicited a release of catecholamines which activated vascular alpha-1, alpha-2 and cardiac beta-1 adrenoceptors. McN-A-343, however, was induced by a release of neurotransmitter stimulation of predominantly vascular alpha-1 and cardiac beta-1 adrenoceptors. Both DMCPM and McN-A-343 were characterized with respect to their ability to stimulate muscarinic-1 (M-1) and/or muscarinic-2 (M-2) receptors. To demonstrate the M-1 component the selective M-1 receptor antagonist pirenzepine was used. M- 2 receptor activation was identified by means of the muscarinic receptor-induced bradycardia after pretreatment with a high dose of atenolol. DMCPM proved to be a mixed M-1/M-2 agonist, in contrast to McN-A-343 which behaved as a rather selective M-1 agonist. The data led us to formulate the hypothesis that the activation of ganglionic M-1 receptors elicits the stimulation of predominantly alpha-1 adrenoceptors in the vascular wall. Activation of ganglionic M-2 receptors may induce an additional stimulation of vascular alpha-2 adrenoceptors. The increase in heart rate seems to be mediated by beta- 1 adrenoceptors only.

Volume 226, Issue 3, pp. 855-860, 09/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics

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