Ameliorative effect of NC-1900, a new AVP4-9 analog, through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze.
The mechanism by which NC-1900, a new pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)) analog, improves spatial memory in rats using an eight-arm radial maze was examined. Even at very low doses (0.2 ng/kg for s.c., 1 microg/kg for p.o., 1 fg for i.c.v.) NC-1900 improved scopolamine-induced impairment of spatial memory. NC-1900 (1 ng/kg, s.c.) also improved impairment of spatial memory induced by pirenzepine, a muscarinic(1) (M(1)) receptor antagonist, and by KN-62, a Ca2+/calmodulin (CaM)-dependent protein kinase II inhibitor. [Pmp(1), Tyr(Me)(2)]-Arg(8)-vasopressin, a vasopressin(1A) (V(1A)) receptor antagonist, and nicardipine, L-type Ca2+ blocker, but not OPC-31260, a V(2) antagonist, suppressed the effect of NC-1900 on scopolamine-induced impairment of spatial memory. A microdialysis study showed that NC-1900 did not affect acetylcholine release in the ventral hippocampus (VH) of intact rats or of scopolamine-treated rats. NC-1900 (1 microM) increased [Ca2+](i) in the VH than in the dorsal hippocampus (DH). Pretreatment with nicardipine (1 microM) and Ca2+ -free conditions inhibited the NC-1900-induced [Ca2+](i) response in the VH. Whereas co-administration of NC-1900 (1 microM) and carbachol (500 microM) increased [Ca2+](i) in the VH. Moreover, nicardipine concentration-dependently inhibited the increase in [Ca2+](i) induced by the co-administration of NC-1900 and carbachol in the VH. These results suggest that NC-1900 activates the V(1A) receptor at the postsynaptic cholinergic nerve, and causes a transient influx of intracellular Ca2+ through L-type Ca2+ channels, to interact with the M(1) receptor. The activation of these Ca2+ -dependent processes induced by NC-1900 may be involved in the positive effect of NC-1900 on scopolamine-induced impairment of spatial memory.
Mishima
K
K
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Tsukikawa
H
H
Miura
I
I
Inada
K
K
Abe
K
K
Matsumoto
Y
Y
Egashira
N
N
Iwasaki
K
K
Fujiwara
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D018680:Cholinergic Antagonists / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D017551:Microdialysis; D009529:Nicardipine / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018680:Cholinergic Antagonists; C115056:NC 1900; D018697:Nootropic Agents; D009842:Oligopeptides; D017483:Receptors, Vasopressin; C089517:vasopressin, 1-(2-mercapto-2,2-(cyclopentamethylene)propionic acid)-2-(O-methyl)Tyr-8-Arg-; D001127:Arginine Vasopressin; C076251:mozavaptan; D010890:Pirenzepine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009529:Nicardipine; D012601:Scopolamine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid