496 Adenylyl cyclase mRNA expression and effects of adenylyl cyclase cascade on contractility in unilateral pregnant rat myometrium

Abstract

496 ADENYLYL CYCLASE MRNA EXPRESSION AND EFFECTS OF ADENYLYL CYCLASE CASCADE ON CONTRACTILITY IN UNILATERAL PREGNANT RAT MYOMETRIUM KIMISATO ASANO 1, TOSHIAKI OKAWA t, HIDENORI TAKAHASHI 1, SATOSHI HASHIMOTO 1, HIROSHI ANBE t, AKIRA SATO I, YURI VEDERNIKOV~, GEORGE SAADE 2, ROBERT GARFIELD 2, YOSUKE SUZUKI t , ISAO MATSUOKA3; ]Fukushima Medical University, Obstetrics and Gynecology, Fukushima; 2University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX; 3Fukushima Medical University, Pharmacology, Fukushima OBJECTIVE: To determine the effect of gestation on adenylyl cyclase (AC) mRNA expression, and on the response to protein kinase C (PKC) and a2 adrenergic agonists in gravid and non-gravid uterine horns of pregnant rats. STUDY DESIGN: Non-pregnan t and day 17 p regnan t Wistar rats were used (n = 6 per group) . In the p regnan t animals, one of the oviducts was ligated before mating in order to result in pregnancy in only one uterine horn. mRNA levels of AC2, AC4, AC6 ad AC9 were determined in the uterine horns with (fetus+) and without (fetus-) fetuses by semi-quantitive reverse transcription-polynaerase chain react ion (RT-PCR). In addit ion, strips of myometr ium fi-om the fetus+ and fetussides were p repa red for isometric tension recording in F-a'ebs-Ringer solution (37°C). The strips were treated with PK-C st inmlant (phorbol myristate acetat: PMA; 1 ~tM) or an a 2 adrenerg ic agonis t (UK-14304; 1 IxM). The changes of contracti l i ty were determined as %change from basal contractile activity. RESULTS: mRNA levels of AC4, AC6 and AC9 were no t significantly different between fetus+ and fetussides on day 47 of gestation. AC2's mRNA levels on the fetusside was significantly lower than the fetus+ side, and were not significantly different than the mRNA levels in the uteri of non-pregnant animals. Uterine contractil i ty was significantly decreased by PMA and UK14304 on the fetus+ side, but was not affected on the fetusside. CONCLUSION: Pregnancy increases AC4, AC6 and AC9 mRNA expression in the uterus by systenfic factors, but the gestational increase in AC2 is dependent on the local presence of pups. AC2 inhibits uterine contractility via a PKC and an ~2 adrenergic receptor in preglmnt myometrium. O f the various adenylyl cyclases, AC2 appears to play the d o m i n a n t role in mainta ining uter ine quiescence in pregnancy. Local factors affecting AC2's expression or function may initiate term or pre term labor. SMFM Abstracts S217