Cholesteryl esters and other neutral lipids in adrenoleukodystrophy brain.

In the present experiments we have measured the liberation of [‘4C]adenosine derivatives and lactate from ‘synaptosome beds’ (de Belleroche & Bradford, 1972), prelabelled with [8-14C]adenosine and superfused with glucose/bicarbonate medium with or without metabolic inhibitors and depolarizing agents. To interpret our findings we have also measured ATP, ADP and AMP of the superfused synaptosomes (Barberis & Mcllwain, 1976). Superfusion of synaptosomes with fluids containing 3 3 m ~ K + gave augmented output of adenosine derivatives and lactate. In the presence of K+, ATP content of synaptosomes decreased and ADP content increased. Such dephosphorylation is reflected by tissue glycolysis, which depends on the degree of phosphorylation of adenine nucleotides and on the inorganic phosphate formed by their breakdown (Lowry et al., 1964). It can be therefore suggested that the dephosphorylation of ATP could have initiated the output of adenine derivatives. Sodium cyanide, added in the superfusion fluid of synaptosome beds at a concentration of 2 . 5 m ~ , increased 3-fold the output of [L4C]adenosine derivatives. This increase in 14C release was concomitant with an increase in lactate output. Again, in the presence of cyanide, synaptosomal ATP content diminished, probably due to the increased I4C release, because ADP and AMP content did not change. Sodium iodoacetate, at a concentration of 2 . 5 m ~ , also increased the release of [14C]adenosine derivatives, by 4-fold, but in this case the lactate output was inhibited and ATP content and total nucleotides were diminished. In the presence of ouabain at a concentration of O . l m ~ , the output of adenosine derivatives increased by 3-fold when the release of lactate was poorly affected. Nevertheless, synaptosomal ATP content decreased and ADP content increased. Veratridine, at a concentration of ~ O P M , increased 4-fold the output of adenosine derivatives and that of lactate. This was accompanied by a great fall in synaptosomal ATP content, and ADP content increased. From these results it is concluded that the release of adenosine derivatives by synaptosomal preparations, in the presence of metabolic inhibitors or depolarizing agents, was not due to a modification of the tissue’s energy metabolism, but to other more specific causes, which affect the metabolism of adenosine derivatives themselves. This research was supported by grants from the Centre National de la Recherche Scientifique (E.R.A. 331) and from the Institut National de la Sante et de la Recherche Medicale