A comparative study of the effects of prostaglandins and H2-receptor antagonists on gastric acid secretion, mucosal blood flow and ulcer formation.
The prostaglandins E2 and 16,16-dimethyl-PGE2 methyl ester were compared with the H2-receptor antagonists burimamide and metiamide for their effects on gastric acid secretion (GAS) and gastric mucosal blood flow (MBF) in rats and dogs, and on ulcer formation in rats. Orally, both 16,16-dimethyl-PGE2 methyl ester (20 microgram/kg) and metiamide (6 mg/kg) were markedly effective inhibitors of GAS stimulated by histamine acid phosphate or pentagastrin in Heidenhain pouch dogs, producing a reduction both in volume of gastric juice and in the concentration of titratable acid. In anaesthetised rats, however, the H2-receptor antagonists, when perfused into the gastric lumen, did not consistently inhibit the increased GAS caused by various secretagogues. In contrast, the prostaglandins, under the same conditions, caused marked inhibition of GAS provoked by all secretagogues. Intravenously, both burimamide and metiamide were effective in inhibiting GAS in rats but were less potent than the prostaglandins. The order of potency was: 16,16-dimethyl-PGE2 methyl ester greater than PGE2 greater than metiamide greater than burimamide. By the oral route, the H2-receptor antagonists were found to be very weak inhibitors of indometacin-induced gastric ulcer in rats, as compared to the prostaglandins. MBF studies in rats and in Heidenhain dogs showed that i.v. or p.o. administration inhibited both GAS and MBF in most cases. The ratio r = [MBF (ml/min)/GAS (mumol H+/min)] was generally increased by both types of compounds, suggesting a preferential effect on GAS.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D003248:Constipation / Q000139:chemically induced / Q000517:prevention & control; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007213:Indomethacin / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy
D006635:Histamine H2 Antagonists; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D009020:Morphine; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin