Abstract
Adenylosuccinase (ASase) deficiency provokes accumulation in body fluids of succinyl-adenosine (S-Ado) and SAICAriboside, the dephosphorylated derivatives of the two substrates of the enzyme. The concentration of both compounds reaches about 100 μM in cerebrospinal fluid, i.e. 10- to 20-fold that In plasma. As an attempt to elucidate the mechanisms of the psychomotor retardation, accompanied by autistic features, recorded in ASase deficiency, interference of S-Ado and SAICAriboside with the binding of adenosine (Ado) to its cerebral receptors was investigated. The binding of 1-2.5 nM (2-3H]Ado to a particular fraction of rat cerebral cortex, in the presence of 0.25-1 μ M deoxycoformycin, was diminished by 56 ± 4 % (mean ± SEM, n=6) by unlabelled Ado (2.5-100 μM). Diminution of binding by ligands for A1 receptors was 24 % with 2.5 μM 2-chloroadenosine, 32 % with 25 μM R-N6-phenylisopropyl-Ado (PIA), 29 % with 25 MM N6-cyclo-hexyl-Ado (CHA) and 36 % with 25 μM N6-cyclopentyl-Ado (CPA). 200 μM 5′-N-ethylcarboxamide-Ado (NECA), a ligand for A2 receptor sites, and 100 μM dipyridamole, a ligand for uptake sites, decreased binding by, respectively, 39 and 33 %.
In contrast, neither S-Ado nor SAICAriboside, both at up to 200 μM concentrations, influenced the binding of [2-3H]Ado. These results indicate that the psychomotor defects observed in ASase deficiency are probably not due to the occupation of cortical membrane sites for Ado by the succinylpurines.
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Françoise Vincent, M., Van Den Berghe, G. 166 INFLUENCE OF SUCCINYLPURINES ON THE BINDING OF ADENOSINE TO A PARTICULATE FRACTION OF RAT CEREBRAL CORTEX. Pediatr Res 24, 138 (1988). https://doi.org/10.1203/00006450-198807000-00190
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DOI: https://doi.org/10.1203/00006450-198807000-00190