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Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca(2+)-releasing second messenger known to date. Here, we report a new role for NAADP in arrhythmogenic Ca(2+) release in cardiac myocytes evoked by β-adrenergic stimulation. Infusion of NAADP into intact cardiac myocytes induced global Ca(2+) signals sensitive to inhibitors of both(More)
Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine(More)
Cyclic ADP-ribose (cADPR, 1, Scheme 1), originally isolated from sea urchins by Lee and co-workers, [1] is a general mediator of intracellular Ca 2+ ion signaling. [2] Analogues of cADPR have been extensively designed and synthesized [3, 4] because of their potential usefulness for investigating the mechanisms of cADPR-mediated Ca 2+ release and application(More)
ii To my wife, Genevieve, for her dedication and example of perseverance. iii ACKNOWLEDGEMENTS I am grateful to all members of my thesis committee, ProfessorGasparoni for their support, guidance and patience. I am indebted to them for going out of their way to make completion of this endeavor possible. I would also be remiss if I did not give thanks to Dr.(More)
Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7(More)
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