T. Brzozowski et al., Involvement of gastrin in gastric secretory and protective actions of N-alpha-methyl histamine, J PHYSL-PAR, 95(1-6), 2001, pp. 89-98
N alpha -methylhistamine (N alpha -MH) is one of an unusual metabolite of h
istamine that was found in Helicobacter pylori-infected stomachs and is bel
ieved to interact with specific histamine H-1, H-2 and H-3-receptors to sti
mulate gastric acid secretion and gastrin release from isolated G-cells but
the effects of Not-MH on gastric mucosal integrity have been little studie
d. This study was designed, (1) to compare the effect of exogenous Na-MH wi
th that of standard histamine on gastric secretion and plasma gastrin level
s in rats equipped with gastric fistula (series A); and (2) to assess the a
ction of N alpha -MH on gastric lesions induced by 100% ethanol (series B)
in rats with or without removal of antral portion of the stomach (antrectom
y). Rats of series B were pretreated intragastrically (i.g.) or intraperito
neally (i.p.) with N alpha -MH or histamine (0.1-2 mg/kg) 30 min prior to 1
00% ethanol (1.5 ml, i.g.) with or without: (1) vehicle (saline); (2) RPR 1
02681 (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 l
esions was determined planimetrically, gastric blood flow (GBF) was assesse
d by H-2-gas clearance method and venous blood was collected for determinat
ion of plasma gastrin levels by radioimmunoassay (RIA). N alpha -MH and his
tamine dose-dependently increased gastric acid output (series A); the dose
increasing this secretion by 50% (ED50) being 2 and 5 mg/kg i.g or i.p., re
spectively, and this effect was accompanied by a significant rise in plasma
gastrin levels. Both, N alpha -MH and histamine attenuated dose-dependentl
y the area of gastric lesions induced by 100% ethanol (series B) while prod
ucing significant rise in the GBF and plasma immunoreactive gastrin increme
nts. These secretory, protective, hiper-gastrinemic and hyperemic effects o
f N alpha -MH and histamine were completely abolished by antrectomy, wherea
s pretreatment with RPR 102681 attenuated significantly the N alpha -MH and
histamine-induced protection against ethanol damage and accompanying hyper
emia. Ranitidine, that produced achlorhydria and a further increase in plas
ma gastrin levels, failed to influence the N alpha -MH and histamine-induce
d protection and accompanying rise in the GBF. We conclude that (1) Na-MH s
timulates gastric acid secretion and exhibit gastroprotective activity agai
nst acid- independent noxious agents in the manner similar to that afforded
by histamine; and (2) this protection involves an enhancement in the gastr
ic microcirculation and release of gastrin acting via specific CCK-B/gastri
n receptors but unexpectively, appears to be unrelated to histamine H-2-rec
eptors. (C) 2001 Published by Elsevier Science Ltd.