Abstract
Nα-methylhistamine (Nα-MH) is one of an unusual metabolite of histamine that was found in Helicobacter pylori-infected stomachs and is believed to interact with specific histamine H 1, H 2 and H 3-receptors to stimulate gastric acid secretion and gastrin release from isolated G-cells but the effects of Nα-MH on gastric mucosal integrity have been little studied. This study was designed; (1) to compare the effect of exogenous Nα-MH with that of standard histamine on gastric secretion and plasma gastrin levels in rats equipped with gastric fistula (series A); and (2) to assess the action of Nα-MH on gastric lesions induced by 100% ethanol (series B) in rats with or without removal of antral portion of the stomach (antrectomy). Rats of series B were pretreated intragastrically (i.g.) or intraperitoneally (i.p.) with Nα-MH or histamine (0.1–2 mg/kg) 30 min prior to 100% ethanol (1.5 ml, i.g.) with or without: (1) vehicle (saline); (2) RPR 102681 (30 mg/kg i.p.), to block CCK-B/gastrin receptors; and (3) ranitidine (40 mg/kg s.c.) to inhibit histamine H 2-receptors. The area of gastric lesions was determined planimetrically, gastric blood flow (GBF) was assessed by H 2-gas clearance method and venous blood was collected for determination of plasma gastrin levels by radioimmunoassay (RIA). Nα-MH and histamine dose-dependently increased gastric acid output (series A); the dose increasing this secretion by 50% (ED 50) being 2 and 5 mg/kg i.g or i.p., respectively, and this effect was accompanied by a significant rise in plasma gastrin levels. Both, Nα-MH and histamine attenuated dose-dependently the area of gastric lesions induced by 100% ethanol (series B) while producing significant rise in the GBF and plasma immunoreactive gastrin increments. These secretory, protective, hipergastrinemic and hyperemic effects of Nα-MH and histamine were completely abolished by antrectomy, whereas pretreatment with RPR 102681 attenuated significantly the Nα-MH and histamine-induced protection against ethanol damage and accompanying hyperemia. Ranitidine, that produced achlorhydria and a further increase in plasma gastrin levels, failed to influence the Nα-MH- and histamine-induced protection and accompanying rise in the GBF. We conclude that (1) Nα-MH stimulates gastric acid secretion and exhibit gastroprotective activity against acid-independent noxious agents in the manner similar to that afforded by histamine; and (2) this protection involves an enhancement in the gastric microcirculation and release of gastrin acting via specific CCK-B/gastrin receptors but unexpectively, appears to be unrelated to histamine H 2-receptors.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call