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

explore the intracellular pathways activated by vasopressin receptorsthe effects of arginine vasopressin (AVP) and its analogs mediating glycine (Gly) induced Cl-currents (l2gly D2) were examined in acutely dissociated rat hoppocampal CA1 neurons using thewhile-cell patch recording technique. AVP and its analogs inhibited l - D2Gly D2 in aconcentration-dependent manner. The inhibitory actions of AVP (4-9) [AVP metabolite] and NC-1900[AVP (4-9) analog] were reversed by avi D21 - D2 receptor antagonist，or pretreatment with BAPTA-AM. In contrast，these blocking procedures had no effect on the DDAVP [V - D22 - D2 agonist] action. AV - D22 - D2 agonistreceptor 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-applicationof the V - D21 - D2 and V - D22 - D2 antagonists. the inhibitory action of NC-1900 was not affected byperfusion with a Ca D12+ D1-free external solutionbut was strongly blocked by thapsigargin. The intercellular application of heparin ofanti-IP - D23 - D2 also blocked the NC-1900 action. Furthermore，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-89和Rp-cAMPS blocked the inhibitory actions of NC-1900和DDAVP. These results suggest thatthe activation of the V - D21 - D2 receptor in the hippocampal neurons induces the production ofIP - D23 D2 which releases Ca - D12+ D1 from the IP - D23 - D2-sensitive Ca - D12+ D1存储sites.Ca D12+ D1 binds to CaM，resulting in the activation of Ca D12+ D1/CaM-sensitive adenylate cyclases. the activation of PKAthrough the adenylate cyclase inhibits l - 2gly 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.