title: Intracellular pathways of V(1) and V(2) receptors activated by arginine vasopressin in rat hippocampal neurons.
abstract: To explore the intracellular pathways activated by vasopressin receptors, the effects of arginine vasopressin (AVP) and its analogues mediating glycine (Gly)-induced Cl(-) currents (I(Gly)) were examined in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch recording technique. AVP and its analogues inhibited I(Gly) in a concentration-dependent manner. The inhibitory actions of AVP(4-9) (AVP metabolite) and NC-1900 (AVP(4-9) analogue) 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 contrast, these blocking procedures had no effect on the 1-desamino-8-D-AVP (DDAVP; V(2) agonist) action. A V(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(1) and V(2) antagonists. The inhibitory action of NC-1900 was not affected by perfusion with a Ca(2+)-free external solution, but was strongly blocked by thapsigargin. The intracellular application of heparin or anti-inositol 1,4,5-triphosphate (IP(3)) also blocked the NC-1900 action. Furthermore, Ca(2+)/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(1) receptor in the hippocampal neurons induces the production of IP(3), which releases Ca(2+) from the IP(3)-sensitive Ca(2+) storage sites. The Ca(2+) binds to CaM, resulting in the activation of Ca(2+/)CaM-sensitive adenylate cyclases. The activation of protein kinase A through the adenylate cyclase inhibits I(Gly).
authors.affiliation: Department of Physiology, Graduate School of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Omura
authors.forename: J
authors.initials: J
authors.lastname: Nabekura
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004791:Enzyme Inhibitors; C115056:NC 1900; D009842:Oligopeptides; D010446:Peptide Fragments; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C076251:mozavaptan; D005576:Colforsin; D004533:Egtazic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003894:Deamino Arginine Vasopressin; D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid; D005998:Glycine