FUNCTIONAL OF CaィイD12+ィエD1-Calmodulin sensitive a denylate cyclase in central neurons

要了解Vasopressin受体激活的内部途径、精氨酸Vasopressin （AVP）及其模拟介导的glycine （Gly）诱导的Cl-currents（Ly D2 Gly D2）在自动分离的大鼠漏斗CA 1神经元使用白细胞补丁记录技术进行测试。AVP and its analogs inhibited ly d2 gly d2 in a concentration-dependent manner。AVP （4-9） [AVP代谢]和NC-1900 [AVP （4-9）模拟]的抑制作用被一个V-Y-D21-Y-D2受体拮抗剂逆转，或用BAPTA-AM预先治疗。In contrast， these blocking procedures had no effect on the DDAVP [VイイD22イエD2 agonist] action。D22受体拮抗剂没有阻止AVP（4-9）或NC-1900的抑制作用，但阻止了DDAVP的作用。AVP的inhibitory action of AVP was completely blocked by the co-application of the V-D21-D2 and V-D22-D2 antagonists。NC-1900的抑制作用没有受到与Ca-I-D12+ I-D1无外部解决方案的影响，但被thapsigargin严重阻塞。反IP序列D23反IP序列的中间应用也被阻断了NC-1900操作。Furthermore，Ca-D12 + Ca-D1/calmodulin （CaM）抑制剂阻断了NC-1900反应，同时凸轮依赖激酶II抑制剂和PKC调制器没有效果。2'， 5'-二氧腺苷、腺苷环酶抑制剂、H-89和Rp-cAMPS阻断了NC-1900和DDAVP的抑制作用。These results suggest that the activation of the V-D21-D2 receptor in the hippocampal neurons induces the production of IP-D23-which releases Ca-D12+-D1 from the IP-D23-sensitive Ca-D12+-D1 storage sites。CaイイD12+イエD1 binds to CaM， resulting in the activation of CaイD12+イエD1/CaM-sensitive腺苷cyclases。The activation of PKA through the adeny？cyclase inhibits ly？D2 Gly？D2.

To explore the intracellular pathways activated by vasopressin receptors, the effects of arginine vasopressin (AVP) and its analogs mediating glycine (Gly)-induced Cl- currents (lィイD2GlyィエD2) were examined in acutely dissociated rat hoppocampal CA1 neurons using the while-cell patch recording technique. AVP and its analogs inhibited lィイD2GlyィエD2 in a concentration-dependent manner. The inhibitory actions of AVP (4-9) [AVP metabolite] and NC-1900 [AVP (4-9) analog] were reversed by a VィイD21ィエD2 receptor antagonist, or pretreatment with BAPTA-AM. In contrast, these blocking procedures had no effect on the DDAVP [VィイD22ィエD2 agonist] action. A VィイD22ィエD2 receptor antagonist did not block the inhibitory action of AVP(4-9) or NC-1900, but blocked that of DDAVP. The inhibitory action of AVP was completely blocked by the co-application of the VィイD21ィエD2 and VィイD22ィエD2 antagonists. The inhibitory action of NC-1900 was not affected by perfusion with a CaィイD12+ィエD1-free external solution, but was strongly blocked by thapsigargin. The intercellular application of heparin of anti-IPィイD23ィエD2 also blocked the NC-1900 action. Furthermore, CaィイD12+ィエD1/calmodulin (CaM) inhibitors blocked the NC-1900 action, while a Cam-dependent kinase II inhibitor and PKC modulators had no effect. 2', 5'-Dideoxyadenosine, an adenylate cyclase inhibitor, H-89 and Rp-cAMPS blocked the inhibitory actions of NC-1900 and DDAVP. These results suggest that the activation of the VィイD21ィエD2 receptor in the hippocampal neurons induces the production of IPィイD23ィエD2 which releases CaィイD12+ィエD1 from the IPィイD23ィエD2-sensitive CaィイD12+ィエD1 storage sites. The CaィイD12+ィエD1 binds to CaM, resulting in the activation of CaィイD12+ィエD1/CaM-sensitive adenylate cyclases. The activation of PKA through the adenylate cyclase inhibits lィイD2GlyィエD2.