EFFECT OF CHOLECYSTOKININ-A RECEPTOR BLOCKADE ON LIPID-INDUCED GASTRIC RELAXATION IN HUMANS

The purpose of this study was to assess the role of endogenous cholecy stokinin (CCK) in regulating fat-induced changes in human gastric rela xation. Proximal gastric pressure-volume relationships were determined in 12 healthy volunteers during a series of gastric distensions, both fasting and after intragastric instillation of 250 ml of 10% Intralip id. All subjects were studied twice, in a randomized, double-blind stu dy, during intravenous infusion of either loxiglumide (CCK-A antagonis t) or saline. For each distension, intragastric pressure and complianc e were determined together with perception intensity. During saline in fusion, Intralipid reduced intragastric pressure (prelipid, 11.7 +/- 0 .8; postlipid, 9.7 +/- 0.6 mmHg; P = 0.002) and increased compliance ( pressure-volume slope values: prelipid, 87.6 +/- 9.7; postlipid, 47.2 +/- 7; P < 0.01). Loxiglumide infusion during fasting exerted no effec t on either intragastric pressure or compliance. After lipid, however, loxiglumide abolished the expected postlipid reduction in intragastri c pressure (prelipid, 12.1 +/- 0.7; postlipid, 11.5 +/- 0.8 mmHg; P = 0.4) but did not consistently abolish the postlipid increase in compli ance. Loxiglumide exerted no effect on the cumulative perception score or on the volume at perception threshold, although it prevented the f at-induced reduction in pressure at perception threshold [control: pre lipid, 15.4 +/- 1.1; postlipid, 10.7 +/- 0.5 (P < 0.05); loxiglumide: prelipid, 13.8 +/- 1.5; postlipid, 12.2 +/- 0.9 (P > 0.05)]. Endogenou s CCK or CCK-A receptors therefore play a role in the fat-induced redu ction of intragastric pressure and might also modulate gastric percept ion after lipid.