Cholinergic-mediated gastric mast cell degranulation with subsequent histamine H1-and H2-receptor activation in stress ulceration in rats.
The effects of atropine, mepyramine, metiamide or NaHCO3 on gastric ulceration, gastric secretion and gastric mast cell degranulation were studied in stressed pylorus-occluded rats. The influence of dexamethasone pretreatment on stress ulcers in animals without pylorus occlusion (intact rats) was also examined. Stress produced a high glandular lesion incidence and ulcer index, and markedly lowered gastric secretion and glandular wall mast cell counts. Injected 0.5 h before stress, atropine, mepyramine or metiamide strongly antagonised ulceration. Atropine or metiamide, but not mepyramine, reduced gastric secretion. Only atropine prevented stress-induced mast cell changes. NaHCO3, given intragastrically before stress, did not prevent ulceration or mast cell degranulation despite complete neutralisation of gastric acid. Dexamethasone-induced gastric mucosal mast cell depletion could reduce stress ulceration. The findings show that stress degranulates stomach mast cells via a cholinergic pathway; released histamine from this source is largely responsbile for gastric ulceration through H1- and H2-receptor effects. Histamine H2-receptor-mediated gastric acid may play only a small contributory role in stress ulcers in rats. The antiulcer mechanisms of histamine H1- and H2-receptor blockade are discussed.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D008785:Metiamide / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D011708:Pylorus / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D013270:Stomach / Q000166:cytology*; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology*; D013312:Stress, Physiological / Q000150:complications / Q000503:physiopathology*
D001639:Bicarbonates; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D008785:Metiamide; D001285:Atropine; D003907:Dexamethasone; D011738:Pyrilamine