| Research Abstract |
Cyclic adenosine diphosphoribose (cyclic ADP-ribose), a metabolite of beta-NAD<@D1+@>D1, was first discovered in sea urchin eggs by Lee and his colleagues as a novel intracellular messenger with Ca<@D12+@>D1-imbilizing activity. It is expected that the cyclic nucleotide mediates Ca<@D12+@>D1release from an inositol 1,4,5-triphosphate-insensitive Ca<@D12+@>D1 store. The cyclic ADP-ribose-synthesizing enzyme, termed ADP-ribosyl cyclase, is especially abundant in Aplysia ovotestis, from which it was purified as a 29 kDa cytoplasmic protein and sequenced. Interestingly, the ADP-ribosyl cyclase has an amino acid sequence homologous to that of human CD38 antigen which is a 46-kDa type II glycoprotein with a single-transmembrane domain. To investigate cyclic ADP-ribose in mammalian brain, we developed radioimmunoassay for the cyclic nucleotide, and obtained the follwing findings.1. Content of cyclic ADFP-ribose in brain (163(]SY.+-。[)9 pmol/g tissue) was the highest amoung rat tissues tested. No correlation of the content and CD38 expression in tissues was observed. 2. The investigation of anatomical distribution of cyclic ADP-ribose in rat brain revealed that the cyclic nucleotide was abundant in all regions of brain tissue (150-250 pmol/g tissue). 3. Cyclic ADP-ribose in rat cerebral cortex was localized mainly in synapostsomal fraction (47% of total) and cytosolic fracion (39%). 4. High contents of cyclic ADP-ribose were detected in frontal cortex (498(]SY.+-。[)59 pmol/g tissue) and parietal cortex (591(]SY.+-。[)92 pmol/g tissue) of human post-mortam brains, which wer 3-4 times higher than that of rat cerebral cortex. 5. There were no sttistically significant difference between the cyclic ADP-ribose contetns in the parietal cortex of controls and those of patients with schizoprenia, dementia of the Alzheimer type or vasclular dementia.
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