Activation of protein kinase C stimulates collagenase production by cultured cells of the cervix of the pregnant guinea pig.
OBJECTIVE
Dilatation of the uterine cervix at parturition is achieved by an estrogen-induced, collagenase-mediated degradation of type I collagen in the cervix. The objective was to test the hypothesis that collagenase production in the cervix of pregnant guinea pig in culture is mediated by activation of protein kinase C.


METHODS
The effects of 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C by phorbol-12-myristate-13-acetate, 1-stearoyl-2-arachidonyl-sn-glycerol and phospholipase C on collagenase production was studied with primary monolayer cultures of cervical cells from Hartley guinea pigs at 50 days' gestation. Results are analyzed for statistical significance with analysis of variance.


RESULTS
Collagenase production is increased twofold to threefold by 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C. The observed stimulation of collagenase production by 17 beta-estradiol and prostaglandin F2 alpha was blocked by the protein kinase C inhibitor 1-(5-isoquinoline sulfonyl) 2-methylpiperazine dihydrochloride.


CONCLUSIONS
Collagenase production in cultured cervical cells of pregnant guinea pig is stimulated by activation of protein kinase C.
Rajabi
M R
MR
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
Solomon
S
S
Poole
A R
AR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D010879:Piperazines; D004958:Estradiol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015237:Dinoprost; D011493:Protein Kinase C; D017364:Collagenases; D013755:Tetradecanoylphorbol Acetate