CD38, a type II transmembrane glycoprotein predominantly expressed in blood cells, is a bifunctional ectoenzyme directly involved in the metabolism of cADP-ribose (cADPR). This is a potent Ca2+ mobilizer in several types of cells. The relationship between the ectocellular site of cADPR production and its intracellular calcium-related functions is poorly understood. Cultured rat cerebellar granule cells showed both enzymic activities of CD38, ADP-ribosyl cyclase and cADPR hydrolase, at a ratio of 16 to 1 respectively, and were immunostained by the anti-(human CD38) monoclonal antibody IB4. In these cells externally added cADPR and β-NAD+ (the precursor of cADPR), but not α-NAD+ or ADP-ribose, enhanced the peak of the depolarization-induced rise in intracellular Ca2+ concentration. This effect was inhibited by 1 µM ryanodine, suggesting a potentiation of calcium-induced calcium release by cADPR. CD38 ectoenzyme activities, ADP-ribosyl cyclase and cADPR hydrolase, were also demonstrated in vivo by microdialysis of adult rat cerebellum, where IB4 bound to granule neurons selectively. Trace amounts (11.5±3.8 nM) of NAD+ were detected by microdialysis sampling and sensitive assays in the basal interstitial fluid of the cerebellum. These results provide a link between ectocellular cADPR turnover and intracellular calcium mobilization in cerebellum.
Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum
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Antonio DE FLORA, Lucrezia GUIDA, Luisa FRANCO, Elena ZOCCHI, Mario PESTARINO, Cesare USAI, Carla MARCHETTI, Ernesto FEDELE, Giovanni FONTANA, Maurizio RAITERI; Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum. Biochem J 1 December 1996; 320 (2): 665–671. doi: https://doi.org/10.1042/bj3200665
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