DIFFERENTIAL ROLE OF M-1 AND M-2 RECEPTORS IN SYMPATHETIC-GANGLIA OF THE PITHED NORMOTENSIVE RAT IN ALPHA-ADRENOCEPTOR-MEDIATED VASOCONSTRICTION

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Abstract
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 atagonist 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 [erythro-DL-1-(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol] 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 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 activation of ganglionic M-1 receptors apparently elicited 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 seemed to be mediated by .beta.1-adrenoceptors only.