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

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 I D2)were examined in acutely dissociated rat hoppocampal CA1neurons using the while-cell patch recording technique.AVP and its analogs inhibited l I D2 Gly D2in 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 I D21个D2 receptor antagonist，or pretreatment with BAPTA-AM.In contrast，these blocking procedures had no effect on the DDAVP[V I D22 ii D2 agonist]action。A V I D 22个D 2 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 I D 21 I D 2 and V I D 22 ii D 2 antagonists.The inhibitory action of NC-1900 was not affected by perfusion with a Ca I D 12个D 1-free external solution，but was strongly blocked by thapsigargin.The intercellular application of heparin of anti-IP I D23 ii D2 also blocked the NC-1900 action。Furthermore，Ca I D12ⅡD1/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-#china_person0#and Rp-cAMPS blocked the inhibitory actions of NC-1900 and DDAVP.These results suggest that the activation of the V I D21文件D2 receptor in the hippocampal neurons induces the production of IP文件D23文件D2 which releases Ca文件D12文件D1from the IP文件D23文件D2-sensitive Ca文件D12文件D1 storage sites.The Ca I D 12 I D 1 binds to CaM，resulting in the activation of Ca I D 12 I D 1/CaM-sensitive adenylate cyclases.The activation of PKA through the adenylate cyclase inhibits l I 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.