Involvement of lactic acidosis in anoxia-induced perturbations of synaptosomal function.
L-Lactate (4-32 mM) added exogenously to resting or depolarised rat forebrain synaptosomes led to a significant decrease in intrasynaptosomal pH. Similarly depolarisation-induced increases in intrasynaptosomal calcium, calcium uptake, and acetylcholine release were all inhibited. These effects mimicked those previously observed in synaptosomes under anoxic conditions and suggest that lactate may be involved in limiting the damage due to calcium accumulation occurring during ischaemia. D-Lactate (added exogenously up to 32 mM) did not produce similar effects on these parameters even though the concentrations of intrasynaptosomal D-lactate reached levels comparable to those obtained with L-lactate (at 8-16 mM exogenous concentration). The results suggest that the mechanism of action of lactate on these parameters is stereospecific for the L-enantiomer. The effect of glucose availability on lactate production was assessed to explore the role of substrate availability on ischaemia/anoxic events. When exogenous glucose was increased (10-60 mM), there was no further increase in lactate production in normoxic synaptosomes, which suggests that glucose is not limiting under these conditions. When glucose was removed, as may occur in complete ischaemia, there was a significant decrease in lactate production after 60 min under anoxic or normoxic conditions. It would seem likely therefore that the mechanism underlying the changes observed in synaptosomes incubated under conditions reflecting complete ischaemia does not involve lactate.
White
E J
EJ
Department of Biochemistry, St. Bartholomew's Hospital Medical College, University of London, England.
Clark
J B
JB
D000140:Acidosis, Lactic / Q000503:physiopathology*; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007773:Lactates / Q000096:biosynthesis / Q000494:pharmacology; D019344:Lactic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D007773:Lactates; D019344:Lactic Acid; D005947:Glucose