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Functional significance of nitric oxide in ionomycin‐evoked [ 3 H]GABA release from mouse cerebral cortical neurons
Author(s) -
Katsura Masashi,
Shuto Keijiro,
Mohri Yutaka,
Shigeto Makoto,
Ohkuma Seitaro
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00810.x
Subject(s) - ionomycin , chemistry , pharmacology , picrotoxin , glutamate receptor , endocrinology , medicine , biochemistry , biology , antagonist , intracellular , receptor
We investigated a role of nitric oxide (NO) on ionomycin‐evoked [ 3 H]GABA release using mouse cerebral cortical neurons. Ionomycin dose‐dependently released [ 3 H]GABA up to 1 µ m . The extent of the release by 0.1 µ m ionomycin was in a range similar to that by 30 m m KCl. The ionomycin (0.1 µ m )‐evoked [ 3 H]GABA release was dose‐dependently inhibited by NO synthase inhibitors and hemoglobin, indicating that the ionomycin‐evoked [ 3 H]GABA release is mediated through NO formation. The inhibition of cGMP formation by 1 H ‐[1,2,4] oxodizao [4,3‐a] quinoxalin‐1‐one (ODQ), a selective inhibitor for NO‐sensitive guanylate cyclase, showed no affects on the ionomycin‐evoked [ 3 H]GABA release. Tetrodotoxin and dibucaine significantly suppressed the ionomycin‐evoked [ 3 H]GABA release and ionomycin increased fluorescence intensity of bis‐oxonol, suggesting the involvement of membrane depolarization in this release. The ionomycin‐evoked [ 3 H]GABA release was maximally reduced by about 50% by GABA uptake inhibitors. The concomitant presence of nifedipine and ω‐agatoxin VIA (ω‐ATX), inhibitors for L‐ and P/Q‐type voltage‐dependent calcium channels, respectively, caused the reduction in the ionomycin‐evoked release by about 50%. The simultaneous addition of nifedipine, ω‐ATX and nipecotic acid completely abolished the release. Although ionomycin released glutamate, (+)‐5‐methyl‐1‐,11‐dihydro‐5H‐dibenzo‐[a,d]cycloheptan‐5,10‐imine (MK‐801) and 6,7‐ dinitroquinoxaline‐2,3‐dione (DNQX) showed no effects on the ionomycin‐induced [ 3 H]GABA release. Based on these results, it is concluded that NO formed by ionomycin plays a critical role in ionomycin‐evoked [ 3 H]GABA release from the neurons.