Potent CNS action of calcitonin to inhibit cysteamine-induced duodenal ulcers in rat.

Intracisternal injection of calcitonin (0.01-5 micrograms) dose dependently prevented the development of duodenal ulcers induced by cysteamine in female rats. By contrast, intravenous infusion of the peptide at a dose 50 times higher than an effective intracisternal dose, had no effect. Intracisternal injection of calcitonin increased by three fold the generation of 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2, in the duodenal mucosa. These studies demonstrated that calcitonin acts within the brain to potently suppress duodenal ulcers induced by cysteamine. The mechanisms of the antiulcer effect may involve changes in prostaglandin generation along with alterations of gastrointestinal secretion and motility associated the central injection of calcitonin. Growing evidence suggests that salmon calcitonin may act as a neuromodulator or neurotransmitter in the central nervous system. Specific binding sites have been demonstrated for calcitonin in the hypothalamus, brain stem and dorsal horn of the spinal cord using homogenate and membrane preparations or in vitro autoradiography methods. The peptide injected into the cerebrospinal fluid (CSF) produces a wide spectrum of biological effects including analgesia, hyperthermia, changes in pituitary hormone release, decrease in food and water intake, locomotor activity, and blood pressure. Numerous studies also demonstrated that calcitonin acts within the brain to markedly influence gastrointestinal secretory and motor function in rats and dogs and gastric ulceration in rats. In particular, intracisternal injection of salmon calcitonin was found very potent to selectively inhibit gastric ulcers elicited by stress, aspirin and central thyrotropin-releasing factor but not by necrotizing agents. In the present study, we further investigated the antiulcer effect of salmon calcitonin using the well established cysteamine experimental model to induce duodenal ulcers in rats. Part of this work has been reported in abstract form.