Walsh J H, Bouzyk M, Rozengurt E
Imperial Cancer Research Fund, London, United Kingdom.
J Cell Physiol. 1993 Aug;156(2):333-40. doi: 10.1002/jcp.1041560216.
Addition of bombesin to Swiss 3T3 cells causes a rapid and transient increase in the intracellular concentration of Ca2+ ([Ca2+]i), which is followed by desensitization to a subsequent addition of the peptide. The concentrations of bombesin used to study this acute cellular desensitization (0.1-0.5 nM) did not deplete the intracellular pool of Ca2+ released by inositol(1,4,5)trisphosphate, as shown by addition of vasopressin after consecutive additions of bombesin. Two lines of evidence support the conclusion that activation of protein kinase C (PKC) does not mediate the acute homologous desensitization of Ca2+ responses induced by bombesin. First, long-term treatment (48 h) of Swiss 3T3 cells with phorbol 12,13-dibutyrate (PDB) to deplete PKC did not prevent homologous desensitization. The responses to second additions of bombesin at 0.1, 0.25, and 0.5 nM were 42%, 26% and 11% of the initial responses, respectively. Second, the PKC inhibitor GF 109203X did not alter homologous desensitization at concentrations that completely prevented the inhibition of Ca2+ mobilization induced by PDB and blocked PDB-mediated phosphorylation of the prominent PKC substrate 80K/MARCKS. We conclude that acute homologous desensitization of Ca2+ responses induced by bombesin occurs through a PKC-independent mechanism.
向瑞士3T3细胞中添加蛙皮素会导致细胞内Ca2+浓度（[Ca2+]i）迅速短暂升高，随后对后续添加的该肽产生脱敏作用。用于研究这种急性细胞脱敏作用的蛙皮素浓度（0.1 - 0.5 nM）并未耗尽由肌醇（1,4,5）三磷酸释放的细胞内Ca2+池，连续添加蛙皮素后再添加血管加压素的实验结果表明了这一点。有两条证据支持蛋白激酶C（PKC）的激活不介导蛙皮素诱导的Ca2+反应急性同源脱敏这一结论。首先，用佛波酯12,13 - 二丁酸（PDB）对瑞士3T3细胞进行长期处理（48小时）以耗尽PKC，并不能阻止同源脱敏。对第二次添加0.1 nM、0.25 nM和0.5 nM蛙皮素的反应分别为初始反应的42%、26%和11%。其次，PKC抑制剂GF 109203X在完全阻止PDB诱导的Ca2+动员抑制并阻断PDB介导的主要PKC底物80K/MARCKS磷酸化的浓度下，并未改变同源脱敏。我们得出结论，蛙皮素诱导的Ca2+反应急性同源脱敏是通过一种不依赖PKC的机制发生的。
