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

采用v-RCDN和PKA抑制剂h -89 （PKA抑制剂）在电压箝位下观察了细胞内信号转导系统抑制剂对局部施加于被测神经元上的Achatina内源性四肽Achatina - 1引起的内向电流（i_< in>）的影响。h -89 （PKA抑制剂）可显著抑制Achatina - 1诱导的i_< in>对PON的作用，而该药物对v-RCDN的i_< in>无效。在生理溶液和H-89存在的情况下，查丁素- i对PON的剂量（压力持续时间）反应研究，以及这些数据的linewever - burk图显示，H-89以非竞争性方式抑制>中的I_<。KT5823 （PKG抑制剂）主要以非竞争性和部分非竞争性的方式抑制了v-RCDN中achatin- 1诱导的>中的I_<，但对PON中>中的I_<无影响。W-7 （calmodulin inhibitor，钙调素抑制剂）非竞争性地抑制PON的>中的I_<，但对v-RCDN的>中的I_<无影响。IBMX（环核苷酸磷酸二酯酶抑制剂）增强了v-RCDN中achatin- 1诱导的>中的I_<，而该药物对PON中>中的I_<无效。然而，IBMX可能对v-RCDN上的achatin- 1受体位点有影响。这些发现表明，多种细胞内信号转导途径介导了achatin- 1诱导的i_< >: PON的>中的i_<通过PKA，可能通过Ca^<2+>/钙调素依赖性蛋白激酶，而v-RCDN的>中的i_<通过pkg。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>中的i_<均无显著影响。

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.