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, 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).
Omura
T
T
Department of Physiology, Graduate School of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Nabekura
J
J
Akaike
N
N
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*
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