DIFFERENTIAL INHIBITORY EFFECTS OF THE IONOPHORE RO2-2985 (X537A) ON CONTRACTILE RESPONSES TO POTASSIUM AND HISTAMINE IN CORONARY-ARTERY SMOOTH-MUSCLE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (1) , 59-63
Abstract
The effects of the ionophore RO2-2985 (X537A) on KCl- and histamine[HM]-induced contractions in porcine coronary vascular smooth muscle were studied in vitro. Cumulative dose-response curves were constructed for KCl and histamine in the presence and absence of RO2-2985. The dose-response curve to KCl in the presence of RO2-2985 was shifted to the right with no change in the maximal response attained. Lineweaver-Burk and Hill plots indicated that responses to KCl involved a positive cooperative interaction between excitation and some step or steps in the contractile event and that RO2-2985 increased this cooperativity. The dose-response curve to [HM] in the presence of the ionophore was significantly shifted to the right with a 40-50% depression in the maximal response. Propranolol inhibited norepinephrine-induced relaxation of KCl-contracted coronary strips but did not affect RO2-2985-induced relaxation. Apparently RO2-2985 competitively inhibits KCl-induced contractions but inhibition of HM-induced contractions are of a mixed mechanism. RO2-2985 does not appear to induce relaxation of coronary artery smooth muscle by liberating endogenous catecholamines. Preliminary evidence supports involvement of prostaglandins in the mechanism of ionophore-induced coronary relaxation.