Adenine nucleotide diphosphates: emerging second messengers acting
via intracellular ca2+ release.
Dousa, Thomas P., Eduardo N. Chini, and Kelly W. Beers.
Renal Pathophysiology Laboratory, Department of Physiology and
Biophysics, Mayo Clinic and Foundation, Mayo Medical School,
Rochester, MN
APStracts 3:0185C, 1996.
Release of calcium (Ca2+) from intracellular stores is a widespread
mechanism in regulations of cell function. Two hitherto unknown
adenine diphosphonucleotides were recently identified, which trigger
Ca2+ release from intracellular stores via channels which are
distinct from the well-known receptor/channel controlled by inositol
1,4,5,-trisphosphate (IP3): cyclic ADP-ribose (cADPR) and nicotinic
acid adenosine dinucleotide phosphate (NAADP). Here we review
synthesis of cADPR from [beta]-NAD, its hydrolysis to adenosine
diphosphoribose (non-cyclic) (ADPR) by cADPR-glycohydrolase as well
as our knowledge about the metabolism of NAADP. The Ca2+ release
triggered by cADPR, NAADP or IP3 can be distinguished by the action
of inhibitors and by desensitization studies. Evidence now emerges
that cADPR synthesis from [beta]-NAD can be stimulated, at least in
some cell types, by all-trans-retinoic acid (atRA) as a first
messenger. Then we review the properties of cADPR and NAADP as
potential second messengers in the intracrine regulation of cell
functions. While their exact role in signaling sequences are not yet
known, cADPR and NAADP are likely to play important intracellular
regulatory function, as extensively documented for the process of egg
fertilization.
Received 12 January 1996; accepted in final form 10 April 1996.
APS Manuscript Number C216-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96