Molecular diversity of adenylyl cyclases in human and rat myometrium. Correlation with global adenylyl cyclase activity during mid- and term pregnancy.
Expression and regulation of myometrial adenylyl cyclases (AC) were studied during pregnancy. Hybridization of poly(A)+ RNA with specific cDNA probes for enzyme types I-IX indicated 1) the presence of transcripts encoding types II-VI and type IX in rat and human, and type VII in rat and 2) the absence of detectable mRNA for types I and VIII in both species. No substantial change was observed in the amount of specific mRNA and basal AC activity from mid-pregnancy to term. However, activation of the alpha2-adrenergic receptor/Gi protein pathway resulted in potentiation of Gs-stimulated AC activity at mid-pregnancy but not at term (Mhaouty, S., Cohen-Tannoudji, J., Bouet-Alard, R., Limon-Boulez, I., Maltier, J. P., and Legrand, C. (1995) J. Biol. Chem. 270, 11012-11016). We demonstrate in the present work that betagamma scavengers transducin-alpha and QEHA peptide abolished this positive input. On the other hand, increasing submicromolar concentrations of free Ca2+, a situation that mimics late term, reduced the forskolin-stimulated AC activity with an IC50 of 3.9 microM. Thus, the presence in myometrium of AC II family (types II, IV, VII) confers ability to G inhibitory proteins to stimulate enzyme activity via betagamma complexes at mid-pregnancy, whereas expression of AC III, V, and VI isoforms confers to the myometrial AC system a high sensitivity to inhibition by Ca2+-dependent processes at term. These data suggest that in the pregnant myometrium, the expression of different species of AC with distinct regulatory properties provides a mechanism for integrating positively or negatively the responses to various hormonal inputs existing either during pregnancy or in late term.
Mhaouty-Kodja
S
S
Laboratoire de Physiologie de la Reproduction, CNRS URA 1449, Université Pierre et Marie Curie, 75252 Paris Cedex 05, France.
Bouet-Alard
R
R
Limon-Boulez
I
I
Maltier
J P
JP
Legrand
C
C
D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000494:pharmacology; D015293:Transducin / Q000494:pharmacology
D013566:Sympathomimetics; D005576:Colforsin; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D015293:Transducin; D000262:Adenylyl Cyclases; D007545:Isoproterenol