Intracellular pathways of V-1 and V-2 receptors activated by arginine vasopressin in rat hippocampal neurons

To explore the intracellular pathways activated by vasopressin receptors, t he effects of arginine vasopressin (AVP) and its analogues mediating glycin e (Gly)induced Cl- currents (I-Gly) were examined in acutely dissociated ra t hippocampal CA1 neurons using the whole-cell patch recording technique. A VP and its analogues inhibited I-Gly in a concentration-dependent manner. T he inhibitory actions of AVP(4-9) (AVP metabolite) and NC-1900 (AVP(4-9) an alogue) were reversed by a V-1 receptor antagonist, or pretreatment with 1, 2-bis(2-amino- 5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid. In contra st, these blocking procedures had no effect on the 1-desamino-8-D-AVP (DDAV P; V-2 agonist) action. A V-1 receptor antagonist did not block the inhibit ory action of AVP(4-9) or NC-1900, but blocked that of DDAVP. The inhibitor y action of AVP was completely blocked by the co-application of the V-1 and V-2 antagonists. The inhibitory action of NC-1900 was not affected by perf usion with a Ca2+-free external solution, but was strongly blocked by thaps igargin. The intracellular application of heparin or anti-inositol 1,4,5-tr iphosphate (IP3) also blocked the NC-1900 action. Furthermore, Ca2+/calmodu lin (CaM) inhibitors blocked the NC-1900 action, while a CaM-dependent kina se II inhibitor and PKC modulators had no effect. 2',5'-Dideoxyadenosine ta n adenylate cyclase inhibitor), H-89, and Rp-cAMPS blocked the inhibitory a ctions of NC-1900 and DDAVP. These results suggest that the activation of t he V-1 receptor in the hippocampal neurons induces the production of IP3 wh ich releases Ca2+ from the IP3-sensitive Ca2+ storage sites. The Ca2+ binds to CaM resulting in the activation of Ca2+/CaM-sensitive adenylate cyclase s, The activation of protein kinase A through the adenylate cyclase inhibit s I-Gly.