Varga G, Papp M, Scarpignato C
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Fundam Clin Pharmacol. 1989;3(3):295-306. doi: 10.1111/j.1472-8206.1989.tb00458.x.
The effect of proglumide and lorglumide, two CCK-receptor antagonists, on caerulein-induced pancreatic secretion and growth was studied in the rat. In anaesthetised animals, caerulein (1 microgram/kg) significantly increased the volume of pancreatic juice and protein output. Lorglumide (5 and 10 mg/kg), administered intraperitoneally 15 min before stimulation, reduced peptide-induced pancreatic exocrine secretion. By contrast, proglumide (100 and 400 mg/kg) was completely ineffective. In experiments dealing with the trophic effect of caerulein, both drugs were administered alone or combined with the peptide (1 microgram/kg) 3 times daily for 5 d. Saline-treated rats served as controls. At the end of the experiment, rats were sacrificed, and growth and composition of pancreatic tissue were determined. Pretreatment of the animals with either proglumide or lorglumide did not affect pancreatic size and composition. Caerulein increased the weight of the pancreas, the total pancreatic protein, trypsin, amylase, and DNA content. After pretreatment with proglumide, all these parameters were not significantly different from those obtained with caerulein alone. In contrast, when lorglumide was given together with caerulein, it significantly reduced caerulein-induced pancreatic growth and decreased enzymatic protein content of the gland. These results show that lorglumide is a much more potent and effective CCK-receptor antagonist than proglumide. Its ability to antagonize the pancreatic secretory and trophic action of a CCK-analogue (i.e. caerulein) supports the view that these physiological actions of CCK are mediated through an interaction of the hormone with specific receptors.
研究了两种胆囊收缩素（CCK）受体拮抗剂丙谷胺和氯谷胺对大鼠蛙皮素诱导的胰腺分泌和生长的影响。在麻醉动物中，蛙皮素（1微克/千克）显著增加了胰液分泌量和蛋白质输出量。在刺激前15分钟腹腔注射氯谷胺（5和10毫克/千克），可减少肽诱导的胰腺外分泌。相比之下，丙谷胺（100和400毫克/千克）则完全无效。在关于蛙皮素营养作用的实验中，两种药物单独给药或与肽（1微克/千克）联合给药，每天3次，持续5天。用生理盐水处理的大鼠作为对照。实验结束时，处死大鼠，测定胰腺组织的生长和组成。用丙谷胺或氯谷胺预处理动物对胰腺大小和组成没有影响。蛙皮素增加了胰腺重量、胰腺总蛋白、胰蛋白酶、淀粉酶和DNA含量。用丙谷胺预处理后，所有这些参数与单独使用蛙皮素时获得的参数没有显著差异。相反，当氯谷胺与蛙皮素一起给药时，它显著降低了蛙皮素诱导的胰腺生长，并降低了胰腺的酶蛋白含量。这些结果表明，氯谷胺是一种比丙谷胺更有效、更具活性的CCK受体拮抗剂。它拮抗CCK类似物（即蛙皮素）的胰腺分泌和营养作用的能力支持了这样一种观点，即CCK的这些生理作用是通过该激素与特定受体的相互作用介导的。
