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Analysis of the presence of postjunctional alpha-2 adrenoceptors in the rat anococcygeus muscle
Authors:M V Ramagopal  H J Leighton
Affiliation:Division of Pharmacology, Glaxo Research Laboratories, Research Triangle Park, North Carolina.
Abstract:When the tone is raised by guanethidine, rat anococcygeus muscle produces inhibitory responses to field stimulation, whose mechanism is not understood properly. The present study is an attempt to investigate the role of alpha adrenoceptors in the field stimulation-induced relaxations in isolated rat anococcygeus muscle. When the tissues are contracted with clonidine, UK-14,304 and low doses of oxymetazoline, field stimulation produced relaxations at lower frequencies, but not in the tissues precontracted with phenylephrine and norepinephrine. Relaxations induced by low frequencies were blocked by idazoxan, but not by phentolamine, prazosin, indomethacin, N-methyl-hydroxylamine, ouabain or 3,4-diminopyridine. When the tone of the muscle is raised by norepinephrine, prazosin reversed the field stimulation-induced contractions to relaxation responses. The data of the present study suggested the possible involvement of alpha-2 adrenoceptors during the field stimulation-induced relaxations of the rat anococcygeus muscle. To analyze and quantitate the alpha-2 adrenoceptor antagonism in the rat anococgygeus muscle, Schild analyses of clonidine-induced contractions against idazoxan were conducted either for idazoxan alone or after partially alkylating the alpha-1 adrenoceptors with phenoxybenzamine and by pharmacologic resultant analysis by blocking the alpha-1 adrenoceptors with prazosin. The Schild regression for idazoxan and pharmacologic resultant analysis suggested that the rat anococcygeus muscle responds to alpha-2 agonists with alpha-1-mediated contractions and idazoxan competes with alpha-1 antagonists for the same site, i.e., alpha-1 adrenoceptor site. However, the atypical Schild regression of idazoxan after partial alkylation with phenoxybenzamine indicated the existence of a second alpha adrenoceptor site in the rat anococcygeus muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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