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Abstract

Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: no role for alpha adrenoceptors.

R M Brazenor and J A Angus
Journal of Pharmacology and Experimental Therapeutics August 1981, 218 (2) 530-536;
R M Brazenor
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Abstract

Studies were performed on isolated canine coronary artery segments to characterize the mechanism of the constrictor response of ergometrine (ergonovine), an agent used to induce coronary vasospasm in patients with variant angina. Changes in isometric tension were measured in coronary ring segments suspended in organ baths at 37 degrees C filled with a buffered salt solution. Single concentration-response curves were obtained in each tissue by cumulative addition of agonist. Maximum responses to 5-hydroxytryptamine (5-HT) were greater than for ergometrine or phenylephrine, but ergometrine had the lowest EC50. Alpha adrenoceptor block by prazosin (10 nM) or the irreversible antagonist benextramine tetrahydrochloride did not affect responses to 5-HT or ergometrine. Cyproheptadine and pizotifen (0.1-1 muM) depressed the ergometrine and 5-HT concentration-response curves with no change in the location of the EC50 values. Methysergide (0.01-1 muM) had concentration-dependent constrictor activity which was noncompetitively antagonized by cyproheptadine, but unaltered by benextramine tetrahydrochloride pretreatment. In addition, methysergide competitively antagonized the 5-HT and ergometrine concentration-response curves. Estimates of methysergide pKB values (-log dissociation constant) from computer analysis were 7.9 and 8.0 for the two agonists, respectively. It is concluded that methysergide is a partial 5-HT agonist, but cyproheptadine and pizotifen are noncompetitive 5-HT antagonists. Ergometrine is a potent 5-HT receptor agonist in canine coronary artery with negligable alpha adrenoceptor agonist activity.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 218, Issue 2
1 Aug 1981
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Abstract

Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: no role for alpha adrenoceptors.

R M Brazenor and J A Angus
Journal of Pharmacology and Experimental Therapeutics August 1, 1981, 218 (2) 530-536;

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Abstract

Ergometrine contracts isolated canine coronary arteries by a serotonergic mechanism: no role for alpha adrenoceptors.

R M Brazenor and J A Angus
Journal of Pharmacology and Experimental Therapeutics August 1, 1981, 218 (2) 530-536;
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