Stimulation by surangin B of endogenous amino acid release from synaptosomes.
The effect of surangin B, an insecticidal natural product coumarin, on presynaptic release of endogenous amino acids was investigated using a purified synaptosomal fraction isolated from mouse brain. Surangin B stimulated the release of glutamic acid (GLU), gamma-aminobutyric acid (GABA), serine, alanine and the aminosulfonic acid taurine from synaptosomes at micromolar concentrations. In all cases, these responses were reduced by removing calcium from the saline and surangin B-evoked release of GLU, GABA, aspartic acid (ASP) and alanine was significantly inhibited by the sodium channel blocker tetrodotoxin. Rotenone (a complex I inhibitor) and carbonyl cyanide chlorophenylhydrazone (CCCP; an uncoupler), were more potent releasers of amino acids from synaptosomes than surangin B, however, carboxin (a complex II-selective inhibitor), was extremely weak to ineffective in this regard. The stimulatory effect of surangin B and complex III-selective inhibitors on release of GLU, GABA, ASP and alanine by synaptosomes was significantly reduced by N,N,N',N'-tetramethyl-p-phenylenediamine, suggesting that blockade of complex III in intraterminal mitochondria is an important effect of this coumarin. Our results demonstrate that surangin B, in common with CCCP and inhibitors of complex I and III, cause release of both neurotransmitter and non-neurotransmitter amino acids from nerve endings in vitro. However, in contrast to most classical agents which interfere selectively with mitochondrial function, the release of endogenous amino acids from synaptosomes by surangin B also involves a moderate extracellular calcium ion-dependent component and relies partially on sodium ion entry into the nerve ending.
D000409:Alanine / Q000187:drug effects / Q000378:metabolism; D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002261:Carboxin / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009097:Multienzyme Complexes / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D012694:Serine / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013654:Taurine / Q000187:drug effects / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D003374:Coumarins; D005659:Fungicides, Industrial; D007306:Insecticides; D009097:Multienzyme Complexes; D014475:Uncoupling Agents; D012402:Rotenone; D013654:Taurine; C480316:surangin B; D018698:Glutamic Acid; D012694:Serine; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D005680:gamma-Aminobutyric Acid; D002261:Carboxin; D000409:Alanine; D002118:Calcium