Shinohara S, Kawasaki K
Division of Pharmacology, Kanzakigawa Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
J Neurochem. 1994 Apr;62(4):1352-6. doi: 10.1046/j.1471-4159.1994.62041352.x.
Desensitization of the cholecystokinin (CCK) octapeptide (CCK-8)-induced rise in intracellular free calcium concentration ([Ca2+]i) was characterized in GH3 cells, a pituitary tumor cell line, which are known to possess CCKB receptor subtype. The CCK-8-induced [Ca2+]i transient was reduced following the initial application of CCK-8. A similar desensitization of the CCK-8-induced response was observed following the first application of thyrotropin-releasing hormone (TRH). By contrast, the TRH-induced response was not desensitized by the preceding application of CCK-8. Desensitization of the CCK-8-induced [Ca2+]i transient was associated with diminished inositol 1,4,5-trisphosphate formation. The recovery of desensitization of the CCK-8-induced response was delayed by a phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A (100 nM). The responsiveness to CCK-8 was also reduced by phorbol 12,13-dibutyrate (PDBu), and this effect of PDBu was completely abolished by preincubation with staurosporine. Staurosporine significantly attenuated the desensitization caused by preincubation with CCK-8, but this effect was too small to attribute the desensitization to the protein kinase C transduction pathway alone. It is likely that desensitization of CCK receptors involves multiple transduction pathways.
在已知具有CCKB受体亚型的垂体肿瘤细胞系GH3细胞中，对胆囊收缩素（CCK）八肽（CCK-8）诱导的细胞内游离钙浓度（[Ca2+]i）升高进行了脱敏特性研究。首次应用CCK-8后，CCK-8诱导的[Ca2+]i瞬变降低。首次应用促甲状腺激素释放激素（TRH）后，观察到CCK-8诱导反应出现类似的脱敏现象。相比之下，先前应用CCK-8并未使TRH诱导的反应脱敏。CCK-8诱导的[Ca2+]i瞬变脱敏与肌醇1,4,5-三磷酸生成减少有关。磷酸丝氨酸/磷酸苏氨酸磷酸酶抑制剂花萼海绵诱癌素A（100 nM）延迟了CCK-8诱导反应脱敏的恢复。佛波醇12,13-二丁酸酯（PDBu）也降低了对CCK-8的反应性，并且用星形孢菌素预孵育可完全消除PDBu的这种作用。星形孢菌素显著减弱了CCK-8预孵育引起的脱敏，但这种作用太小，不能仅将脱敏归因于蛋白激酶C转导途径。CCK受体的脱敏可能涉及多种转导途径。
