Distinct receptors for cholecystokinin and gastrin on canine fundic D-cells.
Distinct receptors for cholecystokinin and gastrin on canine fundic D-cells.
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犬胃底 D 细胞上有不同的缩胆囊素和胃泌素受体。
DOI：
10.1152/ajpgi.1993.264.5.g811
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Yamada,T
中科院分区：
文献类型：
--
作者：
DelValle,J;Chiba,T;Park,J;Yamada,T
尽管胃泌素和胆囊收缩素（CCK）在生物活性羧基末端具有广泛的氨基酸同源性，但这些肽发挥其作用的受体是异质的。在以前的研究中，我们已经研究了胃泌素/CCK肽对分离的犬胃底D-细胞的生物活性，并观察到CCK是比胃泌素更强效和有效的生长抑素释放刺激剂。我们进行了目前的研究，以区分不同的CCK（CCK-A亚型）和胃泌素（CCK-B/胃泌素亚型）受体犬D-细胞。与这一观察结果相一致的是，我们发现CCK-A受体选择性拮抗剂L-364，718剂量依赖性地（10（-11）-10（-7）M）抑制CCK介导的生长抑素释放，但在相同剂量下不改变胃泌素的作用。CCK和胃泌素在从D细胞中置换结合的125 I标记的Leu 15胃泌素-17方面表现出相似的效力。然而，当125 I-CCK八肽（CCK-8）被用作放射性配体，结合标记的一部分不能被替换与胃泌素，但这部分是完全取代与CCK-8。在用高浓度胃泌素预处理的D细胞中，L-364，718能够抑制125 I-CCK-8结合的胃泌素抵抗部分，但CCK-B/胃泌素受体选择性拮抗剂（PD 134308）在高达10（-6）M的剂量下不能影响该结合部分。这些研究描述了犬胃底D细胞上不同CCK-A和CCK-B/胃泌素受体的存在。（250字处删节）
Despite the extensive amino acid homology between gastrin and cholecystokinin (CCK) at the biologically active carboxyl terminus, the receptors through which these peptides exert their action are heterogeneous. In previous studies, we have examined the biological activity of gastrin/CCK peptides on isolated canine fundic D-cells and observed that CCK is a more potent and efficacious stimulant of somatostatin release than gastrin. We performed the present studies to distinguish between distinct CCK (CCK-A subtype) and gastrin (CCK-B/gastrin subtype) receptors on canine D-cells. Consistent with this observation was our finding that the CCK-A receptor selective antagonist L-364,718 dose dependently (10(-11)-10(-7) M) inhibited CCK-mediated somatostatin release but at the same doses did not alter the effect of gastrin. CCK and gastrin exhibited similar potency in displacing bound 125I-labeled Leu15 gastrin-17 from D-cells. However, when 125I-CCK octapeptide (CCK-8) was used as the radioligand, a fraction of the bound label could not be displaced with gastrin, but this fraction was completely displaced with CCK-8. In D-cells pretreated with high concentrations of gastrin, L-364,718 was able to inhibit the gastrin-resistant fraction of 125I-CCK-8 binding, but the CCK-B/gastrin receptor selective antagonist (PD 134308) was unable to influence this fraction of binding in doses as high as 10(-6) M. These studies delineate the presence of distinct CCK-A and CCK-B/gastrin receptors on canine fundic D-cells.(ABSTRACT TRUNCATED AT 250 WORDS)