Modulation of acetylcholine release via GABAA and GABAB receptors in rat striatum.
In order to investigate whether changes in acetylcholine (ACh) release induced by GABA receptors are due to a direct or indirect effect on cholinergic neurons in the striatum, GABAA and GABAB receptor bindings were assayed in the striatum microinjected with ethylcholine mustard aziridinium ion (AF64A), a cholinergic neurotoxin. Intra-striatal injection of a selective concentration of AF64A (10 nmol) reduced GABAA receptor binding without significantly altering GABAB receptor binding. Treatment with a higher, less selective concentration of AF64A (20 nmol) reduced all markers examined. These results suggest that GABAA, but not GABAB receptors, are located on cholinergic neurons in the striatum, and that GABA can directly modulate ACh release through stimulation of GABAA receptors. Findings further suggest that GABA can also indirectly modulate ACh release through stimulation of GABAB receptors located on non-cholinergic neuronal elements in the striatum.
Ikarashi
Y
Y
Department of Neuropsychopharmacology (Tsumura), Gunma University, School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.ikarashi@news.sb.gunma-u.ac.jp
Yuzurihara
M
M
Takahashi
A
A
Hirohisa Ishimaru
Shiobara
T
T
Maruyama
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology; D001640:Bicuculline / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008845:Microinjections; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D014118:Toxins, Biological / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001388:Aziridines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D014118:Toxins, Biological; D014316:Tritium; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine; D001640:Bicuculline