Substance P potentiates calcium channel modulation by somatostatin in chick sympathetic ganglia.
Substance P potentiates calcium channel modulation by somatostatin in chick sympathetic ganglia.
复制标题
P 物质可增强小鸡交感神经节中生长抑素对钙通道的调节作用。
DOI：
10.1152/jn.1994.72.6.2683
复制
发表时间：
1994
影响因子：
2.5
通讯作者：
Siegelbaum,SA
中科院分区：
文献类型：
--
作者：
Golard,A;Role,L;Siegelbaum,SA
1.采用全细胞膜片钳技术测定鸡交感神经节神经元的钙电流。以往的研究表明，生长抑素以电压依赖的方式抑制钙电流(ICA)。生长抑素的作用会迅速脱敏。此外，生长抑素对钙电流的作用被蛋白激酶C(PKC)激活所抑制。由于P物质(SP)可激活鸡交感神经元上的PKC，因此我们在此测试了SP对钙电流的影响以及生长抑素的调节作用。2.在1微米的浓度下，SP对ICa的影响很小，变化很大。3.在5‘-三磷酸鸟苷-S或较高浓度(10微米)的鸟苷存在下，SP以电压依赖的方式抑制ICa，与生长抑素的作用相似。4.SP(1微米)不是抑制生长抑素的作用，而是增强对生长抑素的反应。这种作用只有在生长抑素的反应部分脱敏后才能观察到。SP对生长抑素的非脱敏反应无影响。5.生长抑素反应的脱敏包括其剂量-反应曲线向更高的生长抑素浓度移动以及最大反应的降低。SP似乎选择性地抵消了剂量-反应曲线的移动。6.SP对生长抑素反应的增强作用可被1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7)阻断，但不能被Calphostin C、化合物5、k252a、蛋白激酶C(PKC)19-36或腺苷二磷酸(AMP-PnP)阻断，这表明SP不参与磷酸化，H-7的作用不依赖于激酶抑制。
1. The whole cell patch clamp was used to measure calcium current in isolated chick sympathetic ganglion neurons. Previous results showed that somatostatin inhibits calcium currents (ICa) in a voltage-dependent manner. The effect of somatostatin rapidly desensitizes. In addition, the action of somatostatin on the calcium current is inhibited by activation of protein kinase C (PKC). Because substance P (SP) has been shown to activate PKC in the chick sympathetic neurons, we here test the effects of SP on the calcium current and on the modulatory action of somatostatin. 2. At a concentration of 1 microM, SP had small, variable effects on ICa. 3. SP in the presence of guanosine 5'-triphosphate-gamma-S, or at higher concentrations (10 microM), inhibited ICa in a voltage-dependent manner, similar to the action of somatostatin. 4. Rather than inhibiting the action of somatostatin, SP (1 microM) potentiated the response to somatostatin. This effect of SP was only observed after the response to somatostatin had partially desensitized. SP had no effect on nondesensitized responses to somatostatin. 5. Desensitization of the somatostatin response involved a shift in its dose-response curve toward higher somatostatin concentrations as well as a decrease in the maximal response. SP appears to counteract the shift of the dose-response curve selectively. 6. The potentiation of the somatostatin response by SP is blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), but not by Calphostin C, Compound 5, k252a, protein kinase C (PKC)19-36, or adenylyl-imidodiphosphate (AMP-PNP), suggesting that phosphorylation is not involved and that the H-7 action does not depend on kinase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)