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Central and peripheral gastroprotective and secretory activity of histamine and its N-alpha methyl analog

100%

Brzozowski T., Konturek P. C., Pawlik M., Kwiecien S., Pajdo R., Drozdowicz D., Konturek S. J., Hahn E. G.

Journal of Physiology and Pharmacology. Supplement

2001

tom 52

nr 2

Effect of central and peripheral actions of histamine and its metabolite N-alpha methyl histamine on gastric secretion and acute gastric lesions

80%

Kwiecien S., Brzozowski T., Konturek P. C., Konturek S. J., Pawlik M., Pajdo R., Drozdowicz D., Ptak A., Hahn E. G.

Journal of Physiology and Pharmacology

2001

tom 52

nr 4,1

Nalpha-methylhistamine (Nalpha-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 Nalpha-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 Nalpha-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 Nalpha-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. Nalpha-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 Nalpha-MH inhibited dose-dependently this secretion; the dose attenuating gastric acid output by 50% (ED50) being 4 and 6 µg/kg i.c.v. Both, Nalpha-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 Nalpha-MH and histamine (0.01—5 µg/kg i.c.v.) inhibited ethanol-induced gastric damage whereas higher doses ranging from 10—100 µg/kg of histamine and Nalpha-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 Nalpha-MH inhibits gastric acid secretion and exhibits gastroprotective activity against ethanol in similar manner to that afforded by parenteral and topical histamine and N- MH, 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.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Journal of Physiology and Pharmacology. Supplement

2 Brzozowski T.

2 Drozdowicz D.

2 Hahn E. G.

2 Konturek P. C.

2 Konturek S. J.

2 Kwiecien S.

2 Pajdo R.

2 Pawlik M.

1 Ptak A.

2 2001

Wyniki wyszukiwania

Central and peripheral gastroprotective and secretory activity of histamine and its N-alpha methyl analog

Effect of central and peripheral actions of histamine and its metabolite N-alpha methyl histamine on gastric secretion and acute gastric lesions