A physiological role for cholecystokinin as a regulator of gastrin secretion.

To explore the role of cholecystokinin (CCK) in regulating gastrin secretion in humans, the effect of a CCK antagonist (loxiglumide) on meal-stimulated hormone responses was investigated. Subjects received 500 mL of a liquid test meal in the presence and absence of loxiglumide (22 mumol.kg-1.h-1). In the control experiments, both plasma gastrin and CCK levels increased postprandially. In loxiglumide-treated subjects there was a marked elevation in gastrin (area under the curve, 11,042 +/- 1493/120 min vs. 2156 +/- 281 pg/120 min) and CCK levels compared with the control experiment. These observations were confirmed in experiments with modified sham feeding and gastrin-releasing peptide stimulation in which loxiglumide pretreatment also caused a significant increase in gastrin release compared with saline (P less than 0.05). Further studies with intravenous infusion of gastrin, CCK-8, and CCK-33 with and without loxiglumide showed that the increases in CCK and gastrin during loxiglumide application cannot be explained by alterations in clearance rates. The findings of this study show that postprandial gastrin secretion is influenced by CCK and support the concept of a negative feedback control of gastrin secretion by CCK.