Cholecystokinin in the control of gastric acid secretion in man.
This study was designed to determine the role of cholecystokinin in the control gastric acid secretion in men using loxiglumide, a specific cholecystokinin receptor blocker. Three groups of healthy subjects (A, B, and C) were used; group A--for studies with postprandial gastric secretion, group B--for studies with exogenous gastric secretagogues and group C--for 12 hour intragastric pH-metry. Cephalic phase stimulated by modified sham feeding in group A subjects increased gastric acid secretion to about 50% of pentagastrin maximum and the treatment with loxiglumide in a standard dose (20 mumol/kg iv loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. Gastric acid response to a 5% peptone meal instilled intragastrically greatly enhanced gastric acid secretion and plasma gastrin concentration but the addition of loxiglumide in the standard dose resulted in further increase in both gastric acid and plasma gastrin responses to peptone meal. Infusion of caerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin releasing peptide (25-200 pmol/kg/h) resulted in a dose dependent stimulation of gastric acid secretion reaching about 35% and 25% of maximum attained with pentagastrin. When loxiglumide was added in a standard dose, the acid responses to caerulein and gastrin releasing peptide were further increased two to three fold attaining the peak reaching, respectively, about 100% and 50% of pentagastrin maximum. In group C subjects, 12 hour pH-metry revealed the usual increase in gastric pH after each meal in tests with placebo. Loxiglumide (1200 mg tablets tid, po) resulted in significantly lower pH after each meal and this was accompanied by significantly higher gastrin responses than in placebo tests. We conclude that cholecystokinin released by peptone meal, ordinary meals or gastrin releasing peptide exerts a potent inhibitory influence on gastric acid secretion and gastrin release in men and this inhibition involves subtype A cholecystokinin receptors.
Konturek
J W
JW
Institute of Physiology, University Medical School, Krakow, Poland.
Stoll
R
R
Konturek
S J
SJ
Domschke
W
W
D000328:Adult; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012636:Secretory Rate / Q000187:drug effects
D005755:Gastrins; D010455:Peptides; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D019886:Gastrin-Releasing Peptide; D002108:Ceruletide; D002766:Cholecystokinin; D010418:Pentagastrin; D011377:Proglumide