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

OBJECTIVE: We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in t he pregnant rat. STUDY DESIGN: Rings taken from the middle portions of uterine horns from ra ts at 16 days of gestation were positioned in organ chambers containing phy siologic salt solution bubbled with 5% carbon dioxide in air (37 degrees C, pH similar to 7.4) for isometric tension recording under 2 g passive tensi on. The effects of cumulative concentrations of forskolin and 1,9-dideoxyfo rskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-1 2,330A, 10(-5) mol/L), a nonselective potassium channel blocker (tetrabutyl ammonium, 10(-4) mol/L), or an adenosine triphosphate-dependent potassium c hannel blocker (glibenclamide 10(-5) mol/L) were studied. RESULTS: Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhib it uterine contractions, Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effect ive against 1,9-dideoxyforskolin. CONCLUSION: Activation of adenylate cyclases, as well as adenosine triphosp hate-dependent potassium channels and, to a greater extent, calcium-depende nt potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine con tractions by 1,9-dideoxyforskolin is less than that by forskolin and involv es 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.