Meyer G, Beinborn M, Sewing K F
Institute of General Pharmacology, Hannover Medical School, Germany.
Pharmacology. 1996 Jul;53(1):48-59. doi: 10.1159/000139414.
Cholecystokinin octapeptide (CCK-8s) is an endogenous stimulus of gastric pepsinogen secretion. Previous studies with isolated guinea pig chief cells indicated that this process is mediated through the CCKA receptor subtype, with an additional contribution from CCKB receptors. For comparison, we examined the mechanism of CCK-8s stimulated pepsinogen secretion in a larger nonrodent species, using highly enriched porcine chief cells as a functional in vitro model. Porcine chief cells responded weakly to stimulation by CCK-8s alone, but the efficacy was markedly enhanced in the presence of 10 mumol l-1 forskolin. Under these conditions, pepsinogen secretion was potently stimulated by CCK-8s and the CCKA receptor selective heptapeptide, A-71,378 (EC50 = 4.7 and 33 nmol l-1), but not by CCKB receptor selective agonists. The prototype CCKA receptor selective antagonist L-364,718 blocked pepsinogen secretion with approximately 2,000-fold higher affinity than the CCKB receptor selective analogue, L-365,260. This functional profile was consistent with the affinity rank order of all tested compounds at CCKA-receptor-like [125I]-BH-CCK-8s binding sites in the porcine gastric mucosa. Comparison with cloned CCKA receptors from other species revealed that the receptors mediating pepsinogen secretion in the pig have similar pharmacology, possibly with slight differences in agonist potencies. In contrast to the guinea pig, porcine CCKB receptors appear to have no direct role in pepsinogen secretion.
胆囊收缩素八肽（CCK - 8s）是胃蛋白酶原分泌的内源性刺激物。先前对分离的豚鼠主细胞的研究表明，这一过程是通过CCKA受体亚型介导的，CCKB受体也有额外作用。为作比较，我们使用高度富集的猪主细胞作为功能性体外模型，研究了在一种较大的非啮齿类动物中CCK - 8s刺激胃蛋白酶原分泌的机制。猪主细胞对单独的CCK - 8s刺激反应较弱，但在存在10 μmol l-1福司可林的情况下，效应显著增强。在这些条件下，CCK - 8s和CCKA受体选择性七肽A - 71,378能有效刺激胃蛋白酶原分泌（EC50分别为4.7和33 nmol l-1），但CCKB受体选择性激动剂则无此作用。原型CCKA受体选择性拮抗剂L - 364,718阻断胃蛋白酶原分泌的亲和力比CCKB受体选择性类似物L - 365,260高约2000倍。这种功能特征与所有测试化合物在猪胃黏膜中CCKA受体样[125I]-BH - CCK - 8s结合位点的亲和力排序一致。与其他物种克隆的CCKA受体比较发现，介导猪胃蛋白酶原分泌的受体具有相似的药理学特性，可能在激动剂效力上略有差异。与豚鼠不同，猪的CCKB受体似乎在胃蛋白酶原分泌中没有直接作用。
