D. Lauth et al., 3,4-DIAMINOPYRIDINE-EVOKED NORADRENALINE RELEASE IN RAT HIPPOCAMPAL SLICES - FACILITATION BY ENDOGENOUS OR EXOGENOUS NITRIC-OXIDE, Brain research, 692(1-2), 1995, pp. 174-182
The involvement of nitric oxide (NO) in the evoked release of noradren
aline (NA) was studied in rat hippocampal slices preincubated with [H-
3]NA and stimulated with 3,4-diaminopyridine (3,4-DAP; 200 mu M) for 2
min. The 3,4-DAP-evoked [H-3]overflow was enhanced by the NO synthase
substrate L-arginine, but not by D-arginine; it was reduced by the NO
synthase inhibitor N-G-nitro-L-arginine, which also antagonized the e
ffects of L-arginine. The corresponding nitro derivative of D-arginine
was inactive and unable to block the effects of L-arginine. Also drug
s known to produce NO in-vitro, like sodium nitroprusside (SNP), 3-mor
pholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP)
enhanced the 3,4-DAP-evoked NA release. The NO scavenger hemoglobin s
howed no significant effects when given alone, but reduced or abolishe
d, respectively, the facilitatory effects of SNP, or SNAP and L-argini
ne. The cyclic GMP derivatives 8-Br-cGMP and Sp-8-p-chlorophenylthiogu
anosine-3',5'-c monophosphorothioate (Sp-8-pCPT-cGMPS) also acted faci
litatory, whereas the corresponding Rp-enantiomer of the latter compou
nd was inactive, but antagonized the effect of Sp-8-pCPT-cGMPS. NA rel
ease evoked by 3,4-DAP (10 mu M) from rat hippocampus synaptosomes was
not affected by L-arginine or N-G-nitro-L-arginine but slightly incre
ased by SNAP and Sp-8-pCPT-cGMPS. Antagonists at NMDA, non-NMDA and me
tabotropic glutamate receptors neither affected the 3,4-DAP-evoked NA
release nor the facilitatory effect of L-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 mechan
ism; NMDA receptor stimulation and glutamate release seem not to be in
volved in this phenomenon.