title: Pharmacological characterization of a novel AVP(4-9) binding site in rat hippocampus.
abstract: pGlu-Asn-Cys (Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)), a major metabolite C-terminal fragment of Arginine(8)-vasopressin (AVP), improves the disruption of the learning and memory, and is a far more potent in the mnemonic function than AVP. In this study, we pharmacologically characterized its putative binding site and mechanism of intracellular signaling. Radioligand binding assay showed that [35S]AVP(4-9) could detect specific binding sites in the rat hippocampus membrane preparations, and the binding site was specifically displaced by AVP(4-9) but not by either V(1) or V(2) antagonists. Furthermore, [35S]AVP(4-9) could not detect the cloned rat V(1a), V(1b) and V(2) vasopressin receptors. Even at a low doses (10-100 pM), AVP(4-9) caused an increase in both inositol(1,4, 5)-trisphosphate (Ins(1,4,5)P(3)) and intracellular calcium concentrations ([Ca(2+)](i)) in rat hippocampal cells. The AVP(4-9)-induced [Ca(2+)](i) increase was partially inhibited by the absence of Ca(2+) or by Ca(2+)-channel blocker, suggesting that AVP(4-9) caused the [Ca(2+)](i) increase via release from intracellular calcium store as well as influx from extracellular calcium. For the first time, this study provides evidence to show that AVP(4-9) activates Ins(1,4,5)P(3)/[Ca(2+)](i) pathway through a novel type of receptor in rat hippocampus, which might be potentially important in improving the mnemonic function.
authors.affiliation: Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo, Japan. ynakayama@nch.go.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.forename: Y
authors.initials: Y
authors.lastname: Shimohigashi
authors.forename: S
authors.initials: S
authors.lastname: Tanabe
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology*; D001667:Binding, Competitive; D002118:Calcium / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013462:Sulfur Radioisotopes; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010446:Peptide Fragments; D013462:Sulfur Radioisotopes; D020960:omega-Conotoxins; D001127:Arginine Vasopressin; C075851:omega-conotoxin-MVIIC; D015544:Inositol 1,4,5-Trisphosphate; C045881:argipressin (4-9); D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium