Stimulation of prostaglandin output from rat stomach by hypertonic solutions.

A whole-cell preparation of rat stomach put out appreciable amounts of immunoassayable PGE. Buffers made hypertonic with either sodium chloride or mannitol effected several-fold increases in PGE output, while a comparable osmotic concentration of urea seemed to produce much less stimulation. Enhancement of PGE output by saline--hypertonic buffers was concentration-dependent. It is suggested that the osmolarity of the gastric contents may play a role in regulating gastric PG biosynthesis.

Effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin output from rat stomach and renal papilla in-vitro and ex-vivo.

The effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin (PG) biosynthesis were studied in whole cell preparations of rat renal papilla and stomach in-vitro and ex-vivo. In the ex-vivo experiments a low dose aspirin was a potent inhibitor of PGE output from the stomach but not the renal papilla, while in-vitro renal PGE output was inhibited by aspirin to a greater extent than gastric PGE. Indomethacin and flufenamic acid inhibited both renal papillary and gastric PGE outputs in-vitro and ex-vivo. Paracetamol enhanced PGE output from the stomach more than twice ex-vivo, and to a lesser extent in-vitro. It also augmented PGE output from the papilla ex-vivo but not in-vitro. In view of the possible contribution of cellular organization and pharmacokinetic processes to the ultimate effect, it is suggested that studies on the effects of anti-inflammatory and antipyretic agents on PG biosynthesis should not be restricted to fully in-vitro systems.

The effects of estrus cycle on drug metabolism in the rat.

The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.

Antiulcer activity of clonidine: lack of effect on gastric prostaglandins.

Clonidine and paraaminoclonidine prevented the formation of indomethacin-induced gastric ulcers in female rats. This protective activity was blocked by coadministration of yohimbine. Therefore, the antiulcer activity of clonidine was due to its peripheral alpha-2 agonistic action. Because indomethacin is a prostaglandin synthetase inhibitor, its ulcerogenic effect has been attributed to a state of prostaglandin (PG) deficiency. We therefore investigated the possibility that the protective effect of alpha-2 adrenoceptor agonists could be mediated by stimulation of the biosynthesis of PGs in the stomach. However, the results failed to show increased production of PGE2 or 6-keto-PGF1, either in stomach slices in vitro or in the gastric mucosa of rats pretreated with clonidine, whether indomethacin was used or not. It is concluded that the activity of clonidine in preventing indomethacin-induced gastric erosions in rats is probably not related to prostaglandins.