The effect of lactate on acetylcholine release evoked by various stimuli from Torpedo synaptosomes.
The effect of external lactate on acetylcholine (ACh) release was examined at the nerve electroplaque junction of Torpedo marmorata using cholinergic synaptosomes prepared from the electric organ. Lactate reduced the release of ACh triggered by depolarization of synaptosomes with potassium. However, the release mechanism itself was not affected by lactate since, in its presence, the ACh release induced by different agents such as the calcium ionophore, A23187, or gramicidin D was equal to the release by control synaptosomes (without lactate). A possible site of action for lactate would be the voltage-dependent Ca2+ influx mediated by the natural calcium channel which is thought to couple depolarization and release and which would be bypassed during ionophore-induced Ca2+ entry. An intracellular target was indicated because decreasing the extracellular pH made L(+)lactate a slightly more potent inhibitor. The involvement of a membrane transporter for lactate was suggested by the observation that the D(-) isomer of lactate was less potent than the natural L(+) isomer. The release of endogenous lactate by electric organ prisms was also determined and depolarization with high potassium strongly stimulated L(+)lactate release from prisms. These results suggest that lactate production by stimulated postsynaptic electroplaques may inhibit acetylcholine release from presynaptic nerve terminals, constituting an example of negative feedback.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004557:Electric Organ / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008564:Membrane Potentials; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000502:physiology; D014101:Torpedo
D007473:Ion Channels; D007773:Lactates; D019344:Lactic Acid; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium