Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate)

Author:

BILLINGTON Richard A.12,THURING Jan W.3,CONWAY Stuart J.3,PACKMAN Len4,HOLMES Andrew B.3,GENAZZANI Armando A.12

Affiliation:

1. Department of Pharmacology, Tennis Court Road, University of Cambridge, Cambridge CB2 1PD, U.K.

2. DiSCAFF, University of Piemonte Orientale “A. Avogadro” Via Bovio, 6, Novara, Italy

3. Department of Chemistry, University Chemical Laboratory, Lensfield Road, University of Cambridge, Cambridge CB2 1EW, U.K.

4. Department of Biochemistry, 80 Tennis Court Road, University of Cambridge, Cambridge CB2 1GA, U.K.

Abstract

The pyridine nucleotide NAADP (nicotinic acid–adenine dinucleotide phosphate) has been shown to act as a Ca2+-releasing intracellular messenger in a wide variety of systems from invertebrates to mammals and has been implicated in a number of cellular processes. NAADP is structurally very similar to its precursor, the endogenous coenzyme NADP and while much is known about the reduced form of NADP, NADPH, it is not known whether NAADP can also exist in a reduced state. Here we report that NAADP can be reduced to NAADPH by endogenous cellular enzymes and that NAADPH is functionally inert at the NAADP receptor. These data suggest that NAADPH could represent a mechanism for rapidly inactivating NAADP in cells.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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