AJP - Cell Physiology, Vol 263, Issue 1 C257-C265, Copyright © 1992 by American Physiological Society
Diverse prostaglandin receptors activate distinct signal transduction pathways in rat myometrium
O. Goureau, Z. Tanfin, S. Marc and S. Harbon
Laboratoire d'Endocrinologie et Regulations Cellulaires, Centre National de la Recherche Scientifique URA 1131, Universite Paris Sud, Orsay, France.
Attempts were made to identify prostaglandin (PG) receptors in rat
myometrium, according to the differential rank order of potencies displayed
by the natural PGs and their analogues, both at the level of second
messenger generation and contraction. In estrogen-treated rat myometrium,
PGs [iloprost = PGI2 greater than PGE2 much greater than 16,16-dimethyl
(DM)-PGE2; sulprostone = misoprostol = 0] induced adenosine 3',5'-cyclic
monophosphate generation, indicating the contribution of a PGI2 receptor.
The generation of inositol phosphates was stimulated by PGs (PGF2 alpha
greater than PGD2 much greater than PGE2 = DM-PGE2 much greater than
iloprost greater than sulprostone = misoprostol = 0), reflecting a PGF2
alpha-receptor-mediated process, which was insensitive to pertussis toxin
(PTX). Contractions caused by PGF2 alpha were closely correlated to PGF2
alpha-receptor activation associated with the phospholipase C pathway. By
contrast, contractions evoked by PGE2, equally mimicked by sulprostone and
misoprostol, were abolished by PTX and were independent of phospholipase C
activation. In the pregnant myometrium (day 21), the latter
PGE-receptor-mediated mechanism also contributed to contractions caused by
PGE2 (less than microM concn). Phospholipase C activation was coupled not
only to PGF2 alpha but also to PGE receptors and could be correlated with
contractions induced by PGF2 alpha and PGE2 greater than microM concn). All
PGs tested were coupled to inhibitory G protein-mediated adenylate cyclase
inhibition, displaying an equipotency that did not allow characterization
of the inhibitory PG receptors.
