Konturek J W, Stoll R, Konturek S J, Domschke W
Institute of Physiology, University Medical School, Krakow, Poland.
Gut. 1993 Mar;34(3):321-8. doi: 10.1136/gut.34.3.321.
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.
本研究旨在使用特异性胆囊收缩素受体阻滞剂洛西丁胺，确定胆囊收缩素在男性胃酸分泌调控中的作用。研究使用了三组健康受试者（A组、B组和C组）；A组用于餐后胃分泌研究，B组用于外源性胃泌素研究，C组用于12小时胃内pH值测定。A组受试者通过改良假饲刺激的头期胃酸分泌增加至五肽胃泌素最大分泌量的约50%，给予标准剂量（静脉注射负荷剂量20 μmol/kg，随后以20 μmol/kg/h输注）的洛西丁胺未能影响该分泌。胃内注入5%蛋白胨餐引起的胃酸反应极大地增强了胃酸分泌和血浆胃泌素浓度，但添加标准剂量的洛西丁胺导致对蛋白胨餐的胃酸和血浆胃泌素反应进一步增加。逐渐增加剂量（15 - 120 pmol/kg/h）输注蛙皮素和胃泌素释放肽（25 - 200 pmol/kg/h）导致胃酸分泌呈剂量依赖性刺激，分别达到五肽胃泌素最大分泌量的约35%和25%。当添加标准剂量的洛西丁胺时，对蛙皮素和胃泌素释放肽的酸反应进一步增加2至3倍，分别达到五肽胃泌素最大分泌量的约100%和50%。在C组受试者中，12小时pH值测定显示安慰剂试验中每餐饭后胃pH值通常会升高。洛西丁胺（1200 mg片剂，每日三次，口服）导致每餐饭后pH值显著降低，且与安慰剂试验相比，胃泌素反应显著更高。我们得出结论，蛋白胨餐、普通餐或胃泌素释放肽释放的胆囊收缩素对男性胃酸分泌和胃泌素释放具有强大的抑制作用，且这种抑制涉及A亚型胆囊收缩素受体。
