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 the pregnant rat.


METHODS
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 degrees C, pH approximately 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.
Vedernikov
Y P
YP
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1062, USA.
Syal
A S
AS
Okawa
T
T
Saade
G R
GR
Garfield
R E
RE
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000502:physiology*; D011247:Pregnancy; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D005576:Colforsin; C009405:tetrabutylammonium; D000262:Adenylyl Cyclases; C047983:1,9-dideoxyforskolin