Yu D H, Noguchi M, Zhou Z C, Villanueva M L, Gardner J D, Jensen R T
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Am J Physiol. 1987 Dec;253(6 Pt 1):G793-801. doi: 10.1152/ajpgi.1987.253.6.G793.
Recent studies have demonstrated gastrin receptors in some pancreatic tumors and that gastrin is a potent stimulant of pancreatic Na+-H+ exchange. In the present study we used 125I-labeled gastrin (125I-gastrin) to characterize gastrin receptors on guinea pig pancreatic acini. Binding of 125I-gastrin was temperature dependent, saturable, and specific for gastrin-related peptides. Analysis demonstrated a single class of receptors with high affinity for gastrin (Kd = 1.5 nM) and a binding capacity of 1 fmol/mg protein. Binding of 125I-gastrin was inhibited with the following relative potencies (Kd): cholecystokinin octapeptide (CCK-8) (0.35 nM) greater than gastrin-17-I = gastrin-34-I (1.5 nM) greater than pentagastrin (7 nM) greater than desulfated [des(SO3)]CCK-8 (28 nM) greater than CCK-4 (508 nM) and by the receptor antagonists CBZ-CCK-27-32-NH2 (3.5 microM) greater than proglumide analogue 10 (30 microM) greater than asperlicin (265 microM) greater than Bt2-guanosine 3',5'-cyclic monophosphate (828 micron). In contrast, for both stimulation of enzyme secretion and inhibition of binding of 125I-CCK-8 the relative potencies were CCK-8 much greater than des(SO3)CCK-8 greater than gastrin-17-I = gastrin-34-I greater than pentagastrin greater than CCK-4. For each receptor antagonist the dose-inhibition curve for gastrin-stimulated amylase release was superimpossible with that for CCK-8-stimulated amylase release. Gastrin-17-I at concentrations less than 0.1 microM did not potentiate carbachol or vasoactive intestinal peptide-stimulated amylase secretion and did not affect basal or stimulated adenosine 3',5'-cyclic monophosphate or 45Ca outflux.(ABSTRACT TRUNCATED AT 250 WORDS)
最近的研究已证实在某些胰腺肿瘤中存在胃泌素受体，且胃泌素是胰腺钠氢交换的强效刺激物。在本研究中，我们使用125I标记的胃泌素（125I - 胃泌素）来鉴定豚鼠胰腺腺泡上的胃泌素受体。125I - 胃泌素的结合具有温度依赖性、可饱和性，且对胃泌素相关肽具有特异性。分析表明存在一类对胃泌素具有高亲和力的受体（解离常数Kd = 1.5 nM），结合容量为1 fmol/mg蛋白质。125I - 胃泌素的结合被以下相对效价（Kd）的物质抑制：八肽胆囊收缩素（CCK - 8）（0.35 nM）大于胃泌素 - 17 - I = 胃泌素 - 34 - I（1.5 nM）大于五肽胃泌素（7 nM）大于去硫酸化[des(SO3)]CCK - 8（28 nM）大于CCK - 4（508 nM），并且被受体拮抗剂CBZ - CCK - 27 - 32 - NH2（3.5 microM）大于丙谷胺类似物10（30 microM）大于天冬酰胺素（265 microM）大于Bt2 - 鸟苷3',5' - 环一磷酸（828 microM）抑制。相比之下，对于酶分泌的刺激和125I - CCK - 8结合的抑制，相对效价为CCK - 8远大于des(SO3)CCK - 8大于胃泌素 - 17 - I = 胃泌素 - 34 - I大于五肽胃泌素大于CCK - 4。对于每种受体拮抗剂，胃泌素刺激淀粉酶释放的剂量 - 抑制曲线与CCK - 8刺激淀粉酶释放的剂量 - 抑制曲线重叠。浓度低于0.1 microM的胃泌素 - 17 - I不能增强卡巴胆碱或血管活性肠肽刺激的淀粉酶分泌，且不影响基础或刺激状态下的腺苷3',5' - 环一磷酸或45Ca外流。（摘要截断于250字）
