INTESTINAL PHASE OF HUMAN ANTRO-PYLORO-DUODENAL MOTILITY - CHOLINERGIC AND CCK-MEDIATED REGULATION

In this study the muscarinic receptor antagonist atropine and the chol ecystokinin (CCK)-A receptor antagonist loxiglumide were used to inves tigate the relative importance of cholinergic and CCK-mediated regulat ion of intestinal phase antro-pyloro-duodenal motility. Plasma levels of gastrointestinal hormones [pancreatic polypeptide (PP), gastrin, CC K] were concomitantly determined to estimate biological potency of the doses of the receptor antagonists. In eight healthy male volunteers, a 30-min basal interdigestive period was followed by duodenal perfusio n of a mixed liquid meal for 150 min at 2.6 kcal min(-1) against a bac kground of saline or atropine (5 mu g kg(-1) h(-1)) or loxiglumide (10 mg kg(-1) h(-1)). Antro-pyloro-duodenal motility was continuously mon itored with a sleeve straddling the pylorus. Against a background of s aline, duodenal nutrients persistently stimulated isolated pyloric pre ssure waves. After 60 min, the initially low antral and duodenal contr action rates increased. In the fed state, atropine reduced total numbe r of antral contractions and integrated motility index by 73% (P < 0.0 1) and 76% (P < 0.005), total number of pyloric contractions and integ rated motility index by 43% and 50% (P < 0.05) with inhibition increas ing over time. It did not alter duodenal contraction frequency but dim inished duodenal motility index by 39% (P < 0.05) owing to a reduction in amplitude and duration of contractions. Loxiglumide decreased tota l numbers of antral, pyloric and duodenal contractions by 44% (P < 0.0 5), 74% (P < 0.005) and 41% (P < 0.005) respectively. It reduced cumul ative antral, pyloric and duodenal motility indexes by 60% (P < 0.01), 80% (P < 0.01) and 61% (P < 0.05) respectively. Atropine fully abolis hed PP release to duodenal nutrients whereas loxiglumide reduced it by 60% (P < 0.05). Both atropine and loxiglumide enhanced gastrin releas e whereas only loxiglumide markedly stimulated CCK release. We conclud e that both cholinergic input and endogenous CCK are major stimulatory regulators of antro-pyloroduodenal motility in the intestinal phase. There appears to be a regional heterogeneity of cholinergic and CCK co ntrol. Cholinergic input predominates in the antrum. Both systems are equipotent at the pylorus. CCK predominates in the duodenum. We sugges t that CCK primarily interacts with receptors on cholinergic neurons i n the antropyloric region and primarily affects smooth muscle receptor s in the duodenum.