Arachidonic acid release and inositol lipid metabolism in response to bradykinin and related peptides in human endometrial cells in vitro

Abstract

Prostaglandins of the 2 series are known to play a role in the regulation of menstruation and implantation but, more recently, other vasoactive peptides have been considered as potential regulators of these endometrial processes. The aim of the present study was to investigate the action of the potent vasoactive peptide bradykinin and the structurally related peptide, kallidin, on endometrial function by examining their effect on phosphoinositide hydrolysis and arachidonic acid release from endometrial cells in vitro. Primary cultures of endometrial glands and stromal cells were prelabelled with [ 14C]-arachidonic acid (AA) or [ 3H]-inositol to monitor arachidonic acid release and inositol phosphate accumulation respectively. Bradykinin and kallidin stimulated a dose and time-dependent release of arachidonic acid from stromal cells which, with 100 nmol/L bradykinin, was 30–150% above basal release and maximal at 5 min. Glands were less responsive; 100 nmol/L bradykinin (at 5 min) caused a release of AA of 30–69% above basal level. Bradykinin also stimulated a dose dependent increase in inositol monophosphate production. The maximum response with stromal cells was 8- to 10-fold and with glands, 2-fold (1 and 100 nmol/L bradykinin, respectively). Kallidin was equipotent to bradykinin with respect to both AA and inositol phosphate accumulation. The bradykinin analogue des Arg bradykinin (which acts through the B 1 receptor) released AA from stromal cells but did not alter phosphoinositide hydrolysis, suggesting that these two cellular responses are mediated by different receptors (B 1 and B 2 respectively). There is as yet no evidence for a role for bradykinin in endometrial function, but our findings suggest that bradykinin (or kallidin) could regulate the availability of substrate for prostaglandin synthesis or stimulate second messenger generation and thus control a variety of cellular functions.