Differential role of M-1 and M-2 receptors in sympathetic ganglia of the pithed normotensive rat in alpha adrenoceptor-mediated vasoconstriction.
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.
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000008:administration & dosage; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003714:Denervation; D003971:Diastole / Q000187:drug effects; D004246:Dimethylphenylpiperazinium Iodide / Q000008:administration & dosage; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000008:administration & dosage; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011224:Prazosin / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D046948:Secologanin Tryptamine Alkaloids; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000008:administration & dosage
D000317:Adrenergic alpha-Antagonists; D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D046948:Secologanin Tryptamine Alkaloids; D015016:Yohimbine; D018738:Hexamethonium; C005709:raubasine; D004246:Dimethylphenylpiperazinium Iodide; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D011224:Prazosin