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Cristofol RM, Rodriguez-Farre E: Hippocampal noradrenaline release is modulated by gamma- and delta-hexachlorocyclohexane isomers: which mechanisms are involved?. Eur J Pharmacol. 1994 Feb 11;252(3):305-12.
The differential effects of gamma- and delta-hexachlorocyclohexane isomers on 25 mM K (+)-evoked release of [3H] noradrenaline were studied in hippocampal slices treated with selected agents to activate or block L- and N-type Ca2+ and Na+ voltage-sensitive ion channels, Cl- transport and Ca (2+)-dependent protein activity. At maximally effective concentrations, the L- and N-type Ca2+ channel blockers nifedipine and omega-conotoxin, respectively, and the Na+ channel antagonist tetrodotoxin did not modify the enhancement of K (+)-evoked [3H] noradrenaline release induced by gamma-hexachlorocyclohexane. Likewise, under activation of protein kinase C by phorbol 12,13-dibutyrate (PDB) or inhibition of calmodulin by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), the stimulatory effect of gamma-hexachlorocyclohexane remained almost unchanged. The Cl- transport blocker 4,4-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) significantly reduced the effect of gamma-hexachlorocyclohexane on [3H] noradrenaline release. The enhanced release in the presence of Bay K 8644, the L-type Ca2+ channel activator, was significantly inhibited by nifedipine but not by delta-hexachlorocyclohexane. The combination of omega-conotoxin and tetrodotoxin with delta-hexachlorocyclohexane did not alter the [3H] noradrenaline release effects of each agent alone. Activation of protein kinase C in the presence of delta-hexachlorocyclohexane resulted in a reduction of the delta isomer effect and in a potentiation of the PDB effect. W-7 did not further facilitate the inhibition induced by delta-hexachlorocyclohexane alone. These data suggest that hexachlorocyclohexane isomers may modify K (+)-evoked [3H] noradrenaline release by interacting with presynaptic molecular processes involving changes in Cl- membrane permeability and intracellular Ca2+ homeostasis. |
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