STIMULATION OF PROSTAGLANDIN BIOSYNTHESIS BY DRUGS: EFFECTS in vitro OF SOME DRUGS AFFECTING GUT FUNCTION

Abstract

I Low concentrations of several emetic, purgative or irritant drugs in the absence of added co-factors stimulated conversion of arachidonic acid to prostaglandin E2 and F2a by prostaglandin synthetase extracted from bull seminal vesicles (BSV prostaglandin synthetase). Their effect was dependent on concentration and time. 2 Stimulation of BSV prostaglandin synthetase by apomorphine, aloes, tyramine or zingerone was increased several-fold by addition of reduced glutathione to the incubation medium, whereas hydroquinone, a phenolic co-factor of prostaglandin synthetase caused slight depression. 3 From this finding and from the observation that many of the stimulant drugs possess a phenolic group, whereas their inactive relatives lack such a group, it is suggested that these stimulant drugs act as co-factors for prostaglandin synthetase in place of hydroquinone. 4 Aloes, tyramine, ethanol and quipazine also produced a dose-related increase in resting tone of the isolated fundus of the rat stomach. This increase occurred at concentrations comparable to those effective in stimulating BSV prostaglandin synthetase, and was abolished by acetylsalicylate. 5These findings support the view that certain drugs exert some of their pharmacological effects by stimulating prostaglandin synthetase.

Effects of Β‐adrenoceptor Drug Stimulation on Various Models of Gastric Ulcer in Rats

“…In other experimental animals these agents have been found to increase gastric mucosal blood flow (Curwain & Holton, 1972;Reed & Smy, 1976). Of interest also is the finding that incubation of rat stomach fundus and other tissues with catecholamines in vitro increased the production of prostaglandin E (Pace-Asciak, 1972;Collier, McDonald-Gibson & Seed, 1976) which has the property of protecting gastric mucosa against injury (Robert, Nezamis, Lancaster & Hanchar, 1979).…”

Adrenergic Regulation of Prostaglandin Biosynthesis in Cultured Rabbit Gastric Epithelial Cells.

“…For this purpose, cultured rabbit gastric epithelial cells (RGECs) were used as a PG generating system. Cultured cells can produce considerable amounts of PGs without cofactors, such as reduced glutathione and catechol amines, which are usually used in in vitro experiments (1,10). Since reduced glutathione or catecholamines per se plays important roles in the physiological functions of the stomach (11,12), it is not desirable to use these agents as cofactors when we investigate the effects of drugs on PG biosynthesis in the gastric mucosa.…”

Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation

“…Cap has been found to stimulate prostaglandin formation (Collier et al, 1976) and to induce release of prostaglandins from the rabbit perfused ear artery (Juna et al, 1980) by activation of calcium-dependent phospholipase A2. Moreover, SP release induced by Cap showed tachyphylaxis, but Capinduced prostaglandin formation persisted.…”