Mechanism of cholecystokinin-induced relaxation of the rat stomach

Abstract

This study was designed to investigate the mechanism(s) and the site(s) of action of cholecystokinin (CCK) responsible for the smooth muscle relaxation of the rat stomach. Under xylazine and ketamine anesthesia, an extraluminal force transducer was implanted on the serosal surface of the gastric body to monitor the circular muscle motility. CCK8 (1-100 pmol, i.v.) caused predominantly inhibitory effects (65%) on gastric motility but sometimes no effect (20%), excitatory effects (10%) or biphasic effects (5%) were observed in 125 rats tested. CCK8 consistently caused relaxation in rats pretreated with yohimbine, while CCK8 caused contraction in rats pretreated with propranolol. CCK8-induced relaxation in the presence of yohimbine was abolished by pretreatment with guanethidine, 6-hydroxydopamine, celiac ganglionectomy and hexamethonium but not by VIP antiserum or a nitric oxide (NO) inhibitor. CCK8-induced relaxation was significantly reduced by perineural capsaicin treatment of the celiac ganglia or vagal trunk. Subsequent truncal vagotomy had no effect on CCK8-induced relaxation in rats with perivagal capsaicin treatment, but completely abolished CCK8-induced relaxation in rats with capsaicin treatment of the celiac ganglia. Our present study suggests that CCK8 predominantly stimulates vagal and splanchnic afferents, resulting in vago-splanchnic and splanchno-splanchnic reflexes. Released catecholamine from splanchnic efferents by CCK8 can induce both excitatory and inhibitory reflexes via alpha2 and beta adrenergic receptors located on gastric smooth muscle cells, respectively. These finding may explain some of the variable results reported for the actions of CCK8 on gastric motility.