Cocaine-amphetamine-regulated transcript (CART) acts in the central nervous system to inhibit gastric acid secretion via brain corticotropin-releasing factor system

Recent study has indicated that cocaine-amphetamine-regulated transcript (C ART) is an anorectic chemical in the brain. In the present study, we examin ed the hypothesis that CART may act in the central nervous system to alter gastric function. Food consumption, gastric acid secretion, and gastric emp tying were measured after injection of CART into the cerebrospinal fluid in 24-h fasted Sprague Dawley rats. Central injection of CART inhibited food intake, gastric acid secretion, and gastric emptying. In contrast, ip injec tion of CART failed to inhibit gastric acid secretion and gastric emptying, suggesting that CART acts in the brain to suppress gastric acid secretion and gastric emptying. In the vagotomized animals, centrally administered CA RT did inhibit pentagastrin-stimulated gastric acid secretion. The CART-ind uced acid inhibition was also observed in rats treated with indomethacin, a cyclooxygenase inhibitor. In contrast, pretreatment with central administr ation of a CRF receptor antagonist, alpha-helical CRF9-41, completely block ed the central CART-induced inhibition of gastric acid secretion. All these results suggest that CART acts in the brain to inhibit gastric function vi a brain CRF system. The vagal pathway and the prostaglandin system are not involved in the acid inhibition.