Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Biochemistry, Biology, and Pharmacology of Cyclic Adenosine Diphosphoribose (cADPR)

Author(s): Andreas H. Guse

Affiliation: University Hospital Hamburg-Eppendorf, Center of Experimental Medicine, Institute ofBiochemistry and Molecular Biology I: Cellular Signal Transduction,Martinistr. 52, 20246 Hamburg, Germany.

Abstract:

Cyclic adenosine diphosphoribose (cADPR) is an endogenous Ca2+ mobilizing nucleotide in many cell types and different species covering protozoa, plants and animals, including humans. cADPR is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide (NAD). Since at least some of the ADP-ribosyl cyclases are under the control of receptors for exogenous ligands, cADPR is regarded as a second messenger for Ca2+ signaling. The main intracellular target for cADPR is the ryanodine receptor, but it is unclear whether cADPR elicits Ca2+ release by direct binding or via a binding protein. Derivatives of NAD and cADPR are potent ADP-ribosyl cyclase inhibitors and cADPR antagonists. Since Ca2+ ions are regulators of many diverse cell functions, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation, the cADPR signaling pathway may become a valuable target for pharmaceutical intervention.

Keywords: cyclic adenosine diphosphoribose, adp-ribosyl cyclases, ryanodine receptor, lymphocyte activation

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Article Details

VOLUME: 11
ISSUE: 7
Page: [847 - 855]
Pages: 9
DOI: 10.2174/0929867043455602