N alpha-methylhistamine (N alpha-MH) is one of unusual metabolite of
histamine that was found in Helicobacter pylori-infected stomach and is believed to interact with specific
histamine H1, H2 and H3-receptors to stimulate gastric acid secretion and
gastrin release from isolated G-cells but the effects of N alpha-MH on gastric mucosal integrity have been little studied. This study was designed; 1) to compare the effect of intraperitoneal (i.p.), intracerebroventricular (i.c.v.) and gastric topical (intragastric i.g.) application of exogenous N alpha-MH with that of standard
histamine on gastric secretion in rats equipped with
gastric fistula (series A) and 2) to compare the effect of i.c.v. administration of
histamine and N alpha-MH with that of peripheral (i.p. and i.g.) application of these
amines on gastric lesions induced by 100%
ethanol (series B) in rats with or without
capsaicin-induced deactivation of sensory nerves. The area of gastric lesions was determined planimetrically, gastric blood flow (GBF) was assessed by H2-gas clearance method and venous blood was collected for determination of plasma
gastrin levels by RIA. N alpha-MH and
histamine (0.1-10 mg/kg i.p. or i.g.) dose-dependently increased gastric acid output (series A); whereas i.c.v. administration of
histamine or N alpha-MH inhibited dose-dependently this secretion; the dose attenuating gastric acid output by 50% (ED50) being 4 and 6 microg/kg i.c.v. Both, N alpha-MH and
histamine (2 mg/kg i.p. and i.g.) attenuated significantly the area of gastric lesions induced by 100%
ethanol (series B) while producing significant rise in the GBF and plasma immunoreactive
gastrin increments. Central application of N alpha-MH and
histamine (0.01-5 microg/kg i.c.v.) inhibited
ethanol-induced gastric damage whereas higher doses ranging from 10-100 microg/kg of
histamine and N alpha-MH were significantly less effective.
Capsaicin-induced deactivation of sensory nerves by itself augmented significantly
ethanol damage and attenuated significantly the protective and hyperemic effects of
histamine and its methylated analog applied i.p. but failed to affect significantly those caused by i.c.v. administration of these
amines. We concluded that: 1) central
histamine and N alpha-MH inhibits gastric acid secretion and exhibits gastroprotective activity against
ethanol in similar manner to that afforded by parenteral and topical
histamine and N-alphaMH, 2) central N-alphaMH- and
histamine-induced protection involve the enhancement in gastric microcirculation unrelated to
neuropeptides released from
capsaicin-sensitive afferent nerves, and 3) the major difference between central and peripheral
histamine and its methylated analog is the influence on gastric acid secretion which does not appear to play any major role in gastroprotective activity of these agents.