Mechanism of cholecystokinin-induced relaxation of the rat stomach

This study was designed to investigate the mechanism(s) and the site(s) of action of cholecystokinin (CCK) responsible for the smooth muscle relaxatio n of the rat stomach. Under xylazine and ketamine anesthesia, an extralumin al force transducer was implanted on the serosal surface of the gastric bod y to monitor the circular muscle motility. CCK8 (1-100 pmol, i.v.) caused p redominantly inhibitory effects (65%) on gastric motility but sometimes no effect (20%), excitatory effects (10%) or biphasic effects (5%) were observ ed in 125 rats tested. CCK8 consistently caused relaxation in rats pretreat ed with yohimbine, while CCK8 caused contraction in rats pretreated with pr opranolol. CCK8-induced relaxation in the presence of yohimbine was abolish ed by pretreatment with guanethidine, 6-hydroxydopamine, celiac ganglionect omy and hexamethonium but not by VIP antiserum or a nitric oxide (NO) inhib itor. CCK8-induced relaxation was significantly reduced by perineural capsa icin treatment of the celiac ganglia or vagal trunk. Subsequent truncal vag otomy had no effect on CCK8-induced relaxation in rats with perivagal capsa icin treatment, but completely abolished CCK8-induced relaxation in rats wi th capsaicin treatment of the celiac ganglia. Our present study suggests th at CCK8 predominantly stimulates vagal and splanchnic afferents, resulting in vago-splanchnic and splanchno-splanchnic reflexes. Released catecholamin e from splanchnic efferents by CCK8 can induce both excitatory and inhibito ry reflexes via alpha(2) and beta adrenergic receptors located on gastric s mooth muscle cells, respectively. These finding may explain some of the var iable results reported for the actions of CCK8 on gastric motility. (C) 199 9 Elsevier Science B.V. All rights reserved.