RT Journal Article
SR Electronic
T1 Hormonal Regulation of the Contractile Response Induced by Okadaic Acid in the Rat Uterus
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 841
OP 848
VO 296
IS 3
A1 Mar Trujillo
A1 Luz Candenas
A1 Cristina G. Cintado
A1 Josefina Magraner
A1 Javier Fernandez
A1 Julio D. Martín
A1 Francisco M. Pinto
YR 2001
UL http://jpet.aspetjournals.org/content/296/3/841.abstract
AB The contractile effect of okadaic acid (OA), a highly selective inhibitor of protein serine/threonine phosphatases, was analyzed in the rat uterus during the estrous cycle and during the course of pregnancy. Contractile effects were related to circulating levels of estrogen and progesterone and to mRNA levels of myosin light chain kinase (MLCK) and of myosin light chain protein phosphatase catalytic (PP1-δ) and larger regulatory subunit (MYPT). Both in nonpregnant and pregnant uteri, OA (20 μM) induced a transient contraction, which after plateauing, slowly decreased. In the nonpregnant uterus, the amplitude of this contraction varied at different stages of the estrous cycle, being higher at proestrus and lower at diestrus. In the pregnant uterus, the contraction to OA increased significantly during the course of pregnancy, reaching a maximum in day 21 pregnant rats, and declined after delivery. Whatever the day of pregnancy, the amplitude of the contraction to OA was not significantly modified when obtained in Ca2+-free solution. The magnitude of the OA-induced contraction in spontaneously cycling and pregnant rats was positively correlated to the ratio of estrogen/progesterone serum levels. Reverse transcription-polymerase chain reaction assays on myometrial tissue demonstrated that mRNA expression of PP1-δ and MYPT was higher at early (day 3) than at late (day 21) pregnancy. MLCK mRNA levels were similar in day 3 and day 21 pregnant rats. These data suggest that changes in the expression and activity of myosin phosphatase may contribute to modulating the level of uterine contractile force during the estrous cycle, pregnancy, and labor. The American Society for Pharmacology and Experimental Therapeutics