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 absen...

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Published in:The Journal of biological chemistry 1997-12, Vol.272 (49), p.31100
Main Authors: Mhaouty-Kodja, S, Bouet-Alard, R, Limon-Boulez, I, Maltier, J P, Legrand, C
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - chemistry
Adenylyl Cyclases - metabolism
Animals
Cholera Toxin - pharmacology
Colforsin - pharmacology
Dose-Response Relationship, Drug
Female
Guanosine Triphosphate - pharmacology
Humans
Isoproterenol - pharmacology
Myometrium - drug effects
Myometrium - enzymology
Pregnancy
Pregnancy Trimester, Second
Pregnancy Trimester, Third
Rats
Rats, Sprague-Dawley
Sympathomimetics - pharmacology
Transducin - pharmacology
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.49.31100