The role of nitric oxide in striatal acetylcholine release induced by N-methyl-D-aspartate.
Effect of nitric oxide (NO) on striatal acetylcholine (ACh) release induced by N-methyl-D-aspartate (NMDA) was investigated in freely moving rats by means of microdialysis. NMDA caused a significant increase in ACh release in the striatum, which was blocked by the specific NMDA receptor antagonists, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), indicating that agonist-evoked increase in ACh release in the striatum was through an NMDA receptor-mediated mechanism. NG-monomethyl-L-arginine acetate salt (L-NMMA; a NO synthase inhibitor) facilitated NMDA-evoked increase in ACh release, while L-arginine (the precursor of NO) inhibited the ACh release. The increase by L-NMMA of ACh release induced by the NMDA was also blocked by L-arginine. These results suggest that NO induced by NMDA receptor-mediated mechanism in cholinergic neurons may mediate an inhibitory regulation of ACh release.
Department of Neuropsychopharmacology (Tsumura), Gunma University, School of Medicine, Maebashi, Japan. ikarashi@news.sb.gunma-u.ac.jp
Y
Y
Ikarashi
A
A
Takahashi
H
H
Ishimaru
T
T
Shiobara
Y
Y
Maruyama
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001120:Arginine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D019001:Nitric Oxide Synthase; D000109:Acetylcholine