Down-regulation of G alpha s in human myometrium in term and preterm labor: a mechanism for parturition.
We have previously reported that G alpha s is expressed at considerably higher levels in myometrium taken from pregnant than from nonpregnant women. In the present study we have determined adenylyl cyclase activity in myometrial membranes by measuring the conversion of [alpha-32P]ATP to [32P]cAMP and have measured guanosine triphosphate-binding protein expression by immunoblotting with specific antibodies. Here we report that the increase in G alpha s expression in pregnant myometrium is associated with a significant increase in G alpha s-coupled adenylyl cyclase activity, as estimated by incubating myometrial membranes in the presence of 5'-guanylyl-imidodiphosphate with and without prostaglandin E2. Moreover, in myometrium from women in spontaneous labor G alpha s levels and G alpha s-coupled adenylyl cyclase activity are reduced to the levels observed in nonpregnant tissue. There was no apparent change in forskolin-stimulated adenylyl cyclase activity in nonpregnant, pregnant, and laboring tissue. The increase in G alpha s expression in pregnant myometrium may facilitate agonist-induced cAMP formation, resulting in prolonged relaxation of the uterus during gestation. Down-regulation of G alpha s would decrease the relaxing effect exerted by cAMP and may be a triggering mechanism for the initiation of labor.
Europe-Finner
G N
GN
University of Oxford, Nuffield Department of Obstetrics and Gynecology, Radcliffe Hospital, Headington, Oxford, England.
Phaneuf
S
S
Tolkovsky
A M
AM
Watson
S P
SP
López Bernal
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007743:Labor, Obstetric / Q000378:metabolism*; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000378:metabolism*; D011247:Pregnancy
D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015232:Dinoprostone