Signal transduction systems of achatin-I,a neuropeptide having a D-phenylalanine residue.

用电压钳技术研究了细胞内信号转导系统抑制剂对Achatin-I（<in>Achatin-I，一种含有D-苯丙氨酸残基的Achatin-I）引起的内向电流（I_0）的影响。H-89（PKA抑制剂）能显著抑制Achatin-I引起的PON上的I_0，而H-89<in>对v-RCDN上的I_0则无<in>影响。在生理溶液中和H-89存在下，achatin-I对PON的（压力持续时间）-反应研究以及Lineweaver-Burk图表明，H-89以<in>非竞争性方式抑制I_2。KT 5823 PKG抑制剂<in>主要以非竞争性和部分非竞争性方式抑制achatin-I诱导的v-RCDN的I_2，但对PON的I_2无影响<in>。（钙调素抑制剂）非竞争性抑制PON的I_<in>，而对<in>v-RCDN.IBMX的I_（max）无影响环核苷酸磷酸二酯酶抑制剂（cyclic nucleotide phodiesterase inhibitor，cnPD）能增强achatin-I诱导的<in>v-RCDN的I_2，但对PON的I_2无影响。<in>IBMX可能影响v-RCDN上achatin-I受体位点，提示有多种细胞内信号转导途径介导achatin-I诱导的I_2<in><in>：PON的I_2可能通过PKA和Ca^2+/钙调素依赖性蛋白激酶<in>介导，其他信号转导系统抑制剂包括calphotin C（PKC抑制剂）对v-RCDN和PON的I_2无明显影响<in>。

The effect of intracellular signal transduction system inhibitors on the inward current (I_<in>) caused by achatin-I,an Achatina endogenous tetrapeptide having a D-phenylalanine residue, applied locally onto the neurone tested, were examined under voltage clamp using two identifiable Achatina giant neurone types, v-RCDN and PON.H-89 (PKA inhibitor) markedly suppressed the achatin-I-induced I_<in> on PON, whereas this drug was ineffective on the I_<in> of v-RCDN.Dose (pressure duration)-response study of achatin-I on PON in a physiological solution and in the presence of H-89, and Lineweaver-Burk plot of these data, indicated that H-89 inhibited the I_<in> in noncompetitive manner. KT5823 (PKG inhibitor) suppressed the achatin-I-induced I_<in> of v-RCDN in mainly noncompetitive and partly uncompetitive manners, but this drug had no effect on the I_<in> of PON.W-7 (calmodulin inhibitor) suppressed noncompetitively the I_<in> of PON,but this drug had no effect on the I_<in> of v-RCDN.IBMX (cyclic nucleotide phophodiesterase inhibitor) enhanced the achatin-I-induced I_<in> of v-RCDN,but this drug was ineffective on the I_<in> of PON.However, IBMX might have effects on the achatin-I receptor sites on v-RCDN.These findings suggest multiple intracellular signal transduction pathways mediating the achatin-I-induced I_<in> : the I_<in> of PON is via PKA and probably Ca^<2+>/calmodulin-dependent protein kinase, and the I_<in> of v-RCDN via PKG.Other signal transduction system inhibitors including calphotin C (PKC inhibitor) did not significantly affect the I_<in> of both v-RCDN and PON.