PROTEIN KINASE-C IS NOT NECESSARY FOR PEPTIDE-INDUCED SUPPRESSION OF M-CURRENT OR FOR DESENSITIZATION OF THE PEPTIDE RECEPTORS

PROTEIN KINASE-C IS NOT NECESSARY FOR PEPTIDE-INDUCED SUPPRESSION OF M-CURRENT OR FOR DESENSITIZATION OF THE PEPTIDE RECEPTORS
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DOI:
10.1073/pnas.86.8.2943
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发表时间:
1989-04-01
影响因子:
11.1
通讯作者:
HILLE, B
HILLE, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BOSMA, MM;HILLE, B

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在全细胞电压钳下对蛙交感神经节细胞进行研究,以确定蛋白激酶C(PKC)是否介导多肽诱导的M电流(IM)抑制或多肽受体脱敏。低浓度(10 NM)的鸡促黄体激素释放激素(LHRH)或P物质(SP)抑制IM;此外,较高浓度(1微米)可使受体脱敏。脱敏是同源的(针对多肽),持续至少25分钟。PKC的两种激动剂佛波醇12-肉豆蔻酸酯13-乙酸酯和二辛酰甘油部分抑制IM,阻断对SP的反应,但不阻断对LHRH的反应。PKC抑制剂(假底物星状孢子素和H-7)可阻断PKC激动剂的这两种作用,但不影响SP和LHRH介导的IM抑制和受体脱敏。因此,我们得出结论,PKC不是正常IM抑制或受体脱敏所必需的。
Frog sympathetic ganglion cells were studied under whole-cell voltage clamp to determine whether protein kinase C (PKC) mediates peptide-induced suppression of M current (IM) or desensitization of peptide receptors. Low concentrations (10 nM) of chicken II luteinizing hormone-releasing hormone (LHRH) or substance P (SP) suppressed IM; in addition, higher concentrations (1 .mu.M) desensitized receptors. Desensitization is homologous (specific to the peptide) and lasts at least 25 min. Two stimulators of PKC, phorbol 12-myristate 13-acetate and dioctanoylglycerol, partially depressed IM and occluded the response to SP but not to LHRH. The two actions of PKC stimulators were blocked by PKC inhibitors (staurosporine, a pseudosubstrate peptide, and H-7), but SP- and LHRH-mediated suppression of IM and receptor desensitization were not affected. Thus, we conclude that PKC is not necessary for normal IM suppression or receptor desensitization.