Prostaglandin and histamine involvement in the gastric vasodilator action of pentagastrin.
Male mongrel dogs were anesthetized with 30 mg/kg of pentobarbital and left gastric arterial blood flow (GBF) was measured with electromagnetic flow probes. Pentagastrin, 1microng/kg i.v., produced an initial brief increase in flow followed by a prolonged secondary increase. Histamine, 1 microng/kg, and prostaglandin E2, 0.5 microng/kg, produced monophasic short-lived increases in GBF. The histamine H1 antagonist diphenhydramine and the H2 antagonist metiamide did not affect resting GBF. The prostaglandin synthesis inhibitor, indomethacin, reduced resting GBF by 46%. Responses to histamine were blocked by diphenhydramine by 81% and reduced by indomethacin by 21%. Responses to prostaglandin E2 were reduced by indomethacin by 21%. The primary pentagastrin response was blocked by diphenhydramine by 54%. The secondary pentagastrin response was blocked by both metiamide by 69% and indomethacin by 71%. We conclude that GBF is maintained by a basal production of vasodilatory prostaglandins. Furthermore, pentagastrin can release histamine which by acting on H2 receptors can enhance the production and/or release of prostaglandins to finally mediate an increase in GBF. These actions may partly explain the deleterious effect of indomethacin and the curative effect of prostaglandins on gastric mucosal ulcers.
D000818:Animals; D004155:Diphenhydramine / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000098:blood supply*; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014665:Vasodilator Agents
D011453:Prostaglandins; D011458:Prostaglandins E; D014665:Vasodilator Agents; D008785:Metiamide; D006632:Histamine; D004155:Diphenhydramine; D010418:Pentagastrin; D007213:Indomethacin