CHOLECYSTOKININ IN THE CONTROL OF GASTRIC-ACID SECRETION IN HUMANS

This study was designed to determine the involvement of cholecystokini n (CCK) in the control of gastric acid secretion in men using loxiglum ide, a specific CCK-receptor antagonist. Two groups of healthy subject s (A and B) were used: group A for studies of postprandial gastric sec retion and group B for studies with exogenous gastric secretagogues. T he cephalic phase activated by modified sham feeding (MSF) in group A subjects increased gastric acid secretion to about 36% of pentagastrin maximum, but treatment with loxiglumide in a standard dose (20 mumol/ kg i.v. loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. A 5% peptone meal instilled i.g. (to mimic the gastrointestinal phase) greatly enhanced gastric acid secretion an d plasma gastrin concentration, but the addition of loxiglumide in a s tandard dose resulted in a further increase in both gastric acid and p lasma gastrin responses to the peptone meal. Plasma somatostatin respo nse to the peptone meal was significantly reduced by loxiglumide. Infu sion of cerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin-releasing peptide (GRP) (25-200 pmol/kg/h) resulted in dose-de pendent stimulation of gastric acid secretion, reaching about 35 and 2 5%, of the maximum attained with pentagastrin. When loxiglumide was ad ded the acid responses to cerulein and GRP were further increased by t wo- to threefold. attaining a peak similar to the pentagastrin maximum . Administration of loxiglumide resulted in a significant increase in plasma gastrin response to GRP, whereas plasma somatostatin was not si gnificantly altered by loxiglumide. We conclude that CCK released by a peptone meal or by GRP exerts a potent inhibitory influence on gastri c acid secretion and gastrin release in men and that this inhibition i nvolves subtype A CCK/gastrin CCK receptors.