RELATION BETWEEN CHOLECYSTOKININ AND ANTRAL INNERVATION IN THE CONTROL OF GASTRIC-EMPTYING IN THE RAT

Background-Antral motility and the hormone cholecystokinin (CCK) are m ajor determinants of the rate of gastric emptying. The relation betwee n CCK and antral neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAG) causes selective lesions in gut myenteric neurons after serosal application Aim-To develop a model of antral den ervation using BAC to enable the study of the relation between CCK and antral neurons in regulating gastric emptying. Methods-BAC, vehicle o r the afferent neurotoxin capsaicin were applied to the serosal surfac e of the rat antrum or corpus; neurochemical markers of intrinsic and afferent neurons were detected by using immunohistochemistry and radio immunoassay. Gastric retention of solids was determined after fasting, and emptying of liquids was measured in rats with gastric fistulae. R esults-In BAC treated rats radioimmunoassay of tissue extracts reveale d a dose related specific loss of gastrin releasing peptide, substance P, vasoactive intestinal polypeptide immunoreactivities from the trea ted region, and immunohistochemistry revealed loss of the neuronal mar ker PGP 9.5 and the afferent neuropeptide calcitonin gene related pept ide (CGRP). Adjacent untreated regions were unaffected by BAG, with th e exception that CGRP was depleted in both corpus and antrum after ant ral treatment. After antral BAC treatment fasted rats retained solids for over 48 hours. Moreover, in antrally denervated rats with gastric fistulae, the emptying of saline, acid and peptone was delayed substan tially. The CCK dependent inhibition of gastric emptying of peptone wa s preserved after antral treatment with BAG. Conclusions-Serosal BAC c auses lesions in the innervation of the treated region of the stomach. The innervation of the antrum is essential for normal emptying of bot h liquids and solids, but the inhibition of gastric emptying produced by CCK is not dependent on antral neurons.