Determination of basal acetylcholine release in vivo by rat brain dialysis with a U-shaped cannula: effect of SM-10888, a putative therapeutic drug for Alzheimer's disease.
A U-shaped dialysis cannula was implanted into rat frontal cortex, hippocampus and striatum, and after 1 day for surgical recovery the cannula was perfused with Ringer's solution without any acetylcholinesterase (AChE) inhibitor under freely moving conditions. With a highly sensitive assay method for acetylcholine (ACh), the basal ACh content in the dialysates were detectable in those brain regions for several hours. The basal levels in the frontal cortex, hippocampus and striatum were 82 +/- 9, 72 +/- 4, 70 +/- 8 fmol/20 microliters (mean +/- S.E.M.), respectively. When SM-10888, a novel AChE inhibitor and putative therapeutic drug for Alzheimer's disease, was injected intraperitoneally, ACh in the dialysate of the cortex increased in a dose-dependent manner. Changes in the levels of hippocampal and striatal ACh release evoked by SM-10888 were similar to, but smaller than, that in the cortex. These data suggest that since the present assay method is able to determine in vivo basal ACh release in the dialysate without any AChE inhibitor, it is possible to study the effect of a novel drug such as SM-10888 in the brain regions.
Xu
M
M
Department of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Nakamura
Y
Y
Yamamoto
T
T
Natori
K
K
Irie
T
T
Utsumi
H
H
Kato
T
T
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000585:Aminacrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002404:Catheterization / Q000295:instrumentation; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003956:Dialysis / Q000295:instrumentation; D004867:Equipment Design; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002800:Cholinesterase Inhibitors; C065164:9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine; D000585:Aminacrine; D000109:Acetylcholine