Lloyd K C, Raybould H E, Walsh J H
Research Service, Department of Veterans Affairs, Los Angeles, California.
Am J Physiol. 1992 Sep;263(3 Pt 1):G287-92. doi: 10.1152/ajpgi.1992.263.3.G287.
The purpose of this study was to determine whether selective antagonism of type "A" cholecystokinin (CCK) receptors blocks inhibition of gastric acid secretion produced by CCK and whether this inhibition is mediated through either a somatostatin-dependent pathway or a vago-vagal reflex. Intravenous infusion of CCK (0.04-10 nmol.kg-1.h-1) dose dependently inhibited pentagastrin-stimulated gastric acid secretion in urethan-anesthetized rats, with a 50% inhibitory dose of 0.9 nmol.kg-1.h-1 and a maximum inhibition of approximately 50%. Blockade of type A CCK receptors using the selective type A receptor antagonist MK-329 completely reversed the inhibitory effect produced by a maximal dose (4 nmol.kg-1.h-1) of CCK. Immunoneutralization of endogenous somatostatin by administration of somatostatin monoclonal antibody abolished the inhibition produced by CCK. Concentrations of somatostatin in portal venous plasma were significantly increased after CCK administration; the increase in somatostatin was blocked by pretreatment with MK-329. In contrast, CCK-induced inhibition of gastric acid secretion was unaltered after perivagal capsaicin treatment. These results indicate that CCK inhibits gastric acid secretion in rats by activation of type A CCK receptors and through release of endogenous somatostatin.
本研究的目的是确定“A”型胆囊收缩素（CCK）受体的选择性拮抗作用是否能阻断CCK对胃酸分泌的抑制，以及这种抑制是否通过生长抑素依赖性途径或迷走-迷走反射介导。在乌拉坦麻醉的大鼠中，静脉输注CCK（0.04 - 10 nmol·kg⁻¹·h⁻¹）剂量依赖性地抑制五肽胃泌素刺激的胃酸分泌，半数抑制剂量为0.9 nmol·kg⁻¹·h⁻¹，最大抑制率约为50%。使用选择性A型受体拮抗剂MK - 329阻断A型CCK受体，可完全逆转最大剂量（4 nmol·kg⁻¹·h⁻¹）CCK产生的抑制作用。通过给予生长抑素单克隆抗体对内源性生长抑素进行免疫中和，消除了CCK产生的抑制作用。给予CCK后，门静脉血浆中生长抑素的浓度显著升高；生长抑素的升高被MK - 329预处理所阻断。相反，在迷走神经周围给予辣椒素后，CCK诱导的胃酸分泌抑制作用未改变。这些结果表明，CCK通过激活A型CCK受体并释放内源性生长抑素来抑制大鼠胃酸分泌。
