Adenylate cyclase an potassium channels are involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility

Abstract

Objective:We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat. Study Design:Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5% carbon dioxide in air (37°C, pH −7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9-dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10−5 mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10−4 mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibenclamide 10−5 mol/L) were studied. Results:Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin. Conclusions:Activation of adenylate cyclases, as well as adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine contractions by 1,9-dideoxyforskolin is less than that by forskolin and involves activation of adenylate cyclase and calcium-dependent potassium channels. Whether activation of guanylate cyclase is involved in the effect of the agents on calcium-dependent potassium channels needs further investigation. 1,9-Dideoxyforskolin is not an inactive isomer of forskolin in rat uterine rings.