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 microM) for 2 min. The 3,4-DAP-evoked [3H]overflow was enhanced by the NO synthase substrate L-arginine, but not by D-arginine; it was reduced by the NO synthase inhibitor NG-nitro-L-arginine, which also antagonized the effects of L-arginine. The corresponding nitro derivative of D-arginine was inactive and unable to block the effects of L-arginine. Also drugs known to produce NO in-vitro, like sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1) and S-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 and L-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 microM) from rat hippocampus synaptosomes was not affected by L-arginine or NG-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 of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmakologisches Institut, Universität Freiburg, Federal Republic of Germany.
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Lauth
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Hertting
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Jackisch
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006454:Hemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000077770:Amifampridine; D009638:Norepinephrine