Premium
Effects of amiloride analogues on the production of prostacyclin by aortic endothelial cells
Author(s) -
Boeynaems J.M.,
Demolle D.,
Lagneau C.,
Cragoe E.J.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb14628.x
Subject(s) - amiloride , prostacyclin , chemistry , arachidonic acid , intracellular ph , biochemistry , sodium , medicine , endocrinology , intracellular , biology , enzyme , organic chemistry
1 The release of prostacyclin (PGI 2 ) from bovine aortic endothelial cells stimulated by adenosine 5′‐triphosphate (ATP) was decreased by amiloride analogues bearing alkyl groups on the 5‐amino nitrogen atom, like 5‐(N‐ethyl‐N‐isopropyl)amiloride (EIPA), which are inhibitors of the Na + /H + exchanger. Analogues substituted on a terminal guanidino nitrogen atom were not inhibitory. 2 The release of PGI 2 induced by ATP was not significantly depressed in a Na + ‐poor medium or in a medium acidified to pH 6.9, two conditions known to inhibit the Na + /H + exchanger. 3 Cytoplasmic alkalinization by ammonium chloride did not suppress the inhibitory action of EIPA. By itself, ammonium chloride decreased the response of endothelial cells to ionophore A23187 and ATP, whereas sodium acetate had no effect. 4 EIPA did not decrease the mobilization of free arachidonic acid induced by ATP. It inhibited the conversion of exogenous arachidonate into PGI 2 and prostaglandin E 2 (PGE 2 ). 5 Although the intracellular pH was not measured in this study, it seems unlikely that cytoplasmic alkalinization via the activation of the Na + /H + exchanger plays a significant role in the stimulatory action of ATP on the release of PGI 2 from endothelial cells. The inhibition of that release by EIPA and other amiloride analogues might involve a direct effect on cyclo‐oxygenase, although an action on the reacylation of free arachidonic acid cannot be excluded.