Central nervous system action of calcitonin to alter experimental gastric ulcers in rats.
The central nervous system action of calcitonin to influence various experimental models of gastric ulcers and gastric function was studied in rats fasted for 24 h. Intracisternal injection of salmon calcitonin (5 micrograms) completely suppressed gastric ulcerations induced by exposure to cold restraint stress, intracisternal injection of a stable thyrotropin-releasing hormone analogue, or peroral administration of aspirin. By contrast, intracisternal calcitonin enhanced gastric lesions elicited by peroral administration of 40% ethanol or 0.6 N HCl. Calcitonin action was dose-dependent (0.01-1 microgram) and central nervous system mediated inasmuch as intravenous calcitonin, given at a dose 50-fold higher than that effective intracisternally, did not significantly modify gastric mucosal injuries elicited by aspirin or ethanol. Intracisternal injection of calcitonin at 0.01 microgram inhibited gastric acid output by 90% in pylorus-ligated rats and suppressed gastric emptying of a liquid meal by 63%-94% in doses ranging from 0.01 to 5 micrograms. Prostaglandin generation in the gastric mucosa was not modified by intracisternal injection of calcitonin. These results demonstrate that intracisternal calcitonin acts within the brain to potently prevent ulcer formation elicited by stress, thyrotropin-releasing hormone analogue, or aspirin, but is not cytoprotective against necrotizing agents. Calcitonin action is not related to modification of gastric prostaglandin generation but it may involve the inhibition of gastric secretory and motor function.
Taché
Y
Y
Center for Ulcer Research and Education, Veterans Administration Wadsworth Medical Center, Los Angeles, California.
Kolve
E
E
Maeda-Hagiwara
M
M
Kauffman
G L
GL
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002116:Calcitonin / Q000494:pharmacology / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*
D011453:Prostaglandins; C028815:salmon calcitonin; D002116:Calcitonin