Brevetoxin-3 (PbTx-3) inhibits oxygen consumption and increases Na+ content in mouse liver slices through a tetrodotoxin-sensitive pathway.
To have insights into possible non-neural effects of PbTx-3 (0.07 microgram/ml), its effects on various parameters of hepatic metabolism were evaluated. PbTx-3 inhibits oxygen consumption (QO2) in liver slices by 25 +/- 1%, and increases hepatocyte Na+/K+ ratio by 72 +/- 4%. Ouabain, a Na(+)-K(+)-pump inhibitor, also reduced QO2 by 19 +/- 2% and raised the Na+/K+ ratio by 77 +/- 4%. The effects of PbTx-3 and ouabain on QO2 and Na+/K+ ratio were not additive, suggesting a role for the Na(+)-K(+)-pump in these actions of PbTx-3. However, Na(+)-K(+)-pump activity determinations, using 86Rb as a K+ tracer, did not reveal inhibitory effects of this toxin on the transport system. This indicates that the pump is not a target of PbTx-3. The effect of PbTx-3 on liver slices Na+ content was abolished by the sodium channel blocker tetrodotoxin (0.1 microM). Tetrodotoxin also antagonized the inhibition of oxygen consumption by PbTx-3. These results suggest that in the liver PbTx-3 can induce effects that appear to be similar to those observed in excitable tissue.
Rodriguez
F A
FA
Department of Anatomy, Ponce School of Medicine, Puerto Rico.
Escobales
N
N
Maldonado
C
C
D000704:Analysis of Variance; D000818:Animals; D004141:Dinoflagellida / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D009498:Neurotoxins / Q000633:toxicity*; D010042:Ouabain / Q000633:toxicity; D035964:Oxocins; D010101:Oxygen Consumption / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D000095702:Polyether Toxins
D008387:Marine Toxins; D009498:Neurotoxins; D010042:Ouabain; D035964:Oxocins; D011188:Potassium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013779:Tetrodotoxin; C053342:brevetoxin; D000095702:Polyether Toxins