Nitric oxide-evoked [3H] gamma-aminobutyric acid release is mediated by two distinct release mechanisms.
Mechanisms underlying the release of [3H] gamma-aminobutyric acid (GABA) evoked by nitric oxide (NO) were investigated by use of primary cultured neurons prepared from the mouse cerebral cortex. NO generators such as sodium nitroprusside (SNP) and S-nitroso-N-a etylpenicillamine (SNAP) increased both [3H]GABA release from the neurons and [45Ca2+] influx into the neurons in a dose-dependent manner, which was significantly diminished by hemoglobin. The removal of Ca2+ significantly reduced the NO-induced [3H]GABA release by about 50%. Nipecotic acid and 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1, 2, 5, 6-tetrahydro-3- pyridinecarboxylic acid (NO-711), GABA uptake inhibitors dose-dependently inhibited the NO-evoked [3H]GABA release in either the presence or absence of Ca2+. The concentration of these GABA uptake inhibitors to suppress the NO-induced release of [3H]GABA was sufficiently lower than that to exhibit the inhibition of [3H]GABA transport into the neurons. In addition, the NO-evoked [3H]GABA release was reduced by approximately 50% when total Na+ in incubation buffer was replaced with equimolar choline, and was also completely abolished by the removal of both Ca2+ and Na+. These results indicate that the release of [3H]GABA evoked by NO is mediated by two release mechanisms, a Ca2+ -dependent release system and the reverse process of the Ca2+ -independent and Na+ -dependent carrier-mediated GABA uptake system.
Ohkuma
S
S
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Katsura
M
M
Chen
D Z
DZ
Narihara
H
H
Kuriyama
K
K
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009557:Nipecotic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D026423:S-Nitroso-N-Acetylpenicillamine; D012964:Sodium / Q000378:metabolism; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009557:Nipecotic Acids; D010091:Oximes; D014316:Tritium; C078793:NNC 711; D009599:Nitroprusside; C030278:nipecotic acid; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D011392:Proline; D012964:Sodium; C010983:homoproline; D010396:Penicillamine; D002118:Calcium