Modulation of GABA Release by Second Messenger Substances and NO in Mouse Brain Stem Slices Under Normal and Ischemic Conditions

Authors: Saransaari, Pirjo; Oja, Simo

Source: Neurochemical Research, Volume 31, Number 11, November 2006 , pp. 1317-1325(9)

Publisher: Springer

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GABA is the inhibitory neurotransmitter in most brain stem nuclei. The properties of release of preloaded [3H]GABA were now investigated with slices from the mouse brain stem under normal and ischemic (oxygen and glucose deprivation) conditions, using a superfusion system. The ischemic GABA release increased about fourfold in comparison with normal conditions. The tyrosine kinase inhibitor genistein had no effect on GABA release, while the phospholipase inhibitor quinacrine reduced both the basal and K+-evoked release in normoxia and ischemia. The activator of protein kinase C (PKC) 4-phorbol 12-myristate 13-acetate had no effects on the releases, whereas the PKC inhibitor chelerythrine reduced the basal release in ischemia. When the cyclic guanosine monophosphate (cGMP) levels were increased by superfusion with zaprinast and other phosphodiesterase inhibitors, GABA release was reduced under normal conditions. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine (HA) enhanced the basal and K+-stimulated release by acting directly on presynaptic terminals. Under ischemic conditions GABA release was enhanced when cGMP levels were increased by zaprinast. This effect was confirmed by inhibition of the release by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The NO-producing agents SNAP, HA, and sodium nitroprusside potentiated GABA release in ischemia. These effects were reduced by the NO synthase inhibitor NG-nitro-l-arginine, but not by ODQ. The results show that particularly NO and cGMP regulate both normal and ischemic GABA release in the brain stem. Their effects are however complex.

Keywords: GABA release; ischemia; mouse brain stem; nitric oxide; second messengers; tissue slices

Document Type: Research Article


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Publication date: November 1, 2006

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