3,4-diaminopyridine-evoked noradrenaline release in rat hippocampal slices: facilitation by endogenous or exogenous nitric oxide

The involvement of nitric oxide (NO) in the evoked release of noradrenaline (NA) was studied in rat hippocampal slices preincubated with [³H]NA and stimulated with 3,4-diaminopyridine (3,4-DAP; 200 μM) for 2 min. The 3,4-DAP-evoked [³H]overflow was enhanced by the NO synthase substratel-arginine, but not byd-arginine; it was reduced by the NO synthase inhibitorN^G-mitro-l-arginine, whichl-arginine. Also drugs known to produce NO in-vitro, like sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1) andS-nitroso-N-acetylpenicillamine (SNAP) enhanced the 3,4-DAP-evoked NA release. The NO scavenger hemoglobin showed no significant effects when given alone, but reduced or abolished, respectively, the facilitatory effects of SNP, or SNAP andl-arginine. The cyclic GMP derivatives 8-Br-cGMP and Sp-8-p-chlorophenylthioguanosine-3′,5′-cyclic monophosphorothioate (Sp-8-pCPT-cGMPS) also acted facilitatory, whereas the corresponding Rp-enantiomer of the latter compound was inactive, but antagonized the effect of Sp-8-pCPT-cGMPS. NA release evoked by 3,4-DAP (10 μM) from rat hippocampus synaptosomes was not affected byl-arginine orN^G-nitro-l-arginine but slightly increased by SNAP and Sp-8-pCPT-cGMPS. Antagonists at NMDA, non-NMDA and metabotropic glutamate receptors neither affected the 3,4-DAP-evoked NA release nor the facilitatory effect ofl-arginine. From these findings we conclude that endogenously formed NO facilitates 3,4-DAP-evoked NA release in rat hippocampus, possibly by a cyclic GMP dependent mechanism; NMDA receptor stimulation and glutamate release seem not to be involved in this phenomenon.