Cyclic ADP-ribose as a universal calcium signal molecule in the nervous system.
beta-NAD(+) is as abundant as ATP in neuronal cells. beta-NAD(+) functions not only as a coenzyme but also as a substrate. beta-NAD(+)-utilizing enzymes are involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a universal Ca(2+) mobilizer from intracellular stores, from beta-NAD(+). cADPR acts through activation/modulation of ryanodine receptor Ca(2+) releasing Ca(2+) channels. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Moreover, cADPR/CD38 is critical in oxytocin release from the hypothalamic cell dendrites and nerve terminals in the posterior pituitary. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or synthetic cADPR analogues may provide new therapeutic opportunities for treatment of neurodevelopmental disorders.
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan. haruhiro@med.kanazawa-u.ac.jp
Haruhiro
H
Higashida
Alla B
AB
Salmina
Raissa Ya
RY
Olovyannikova
Minako
M
Hashii
Shigeru
S
Yokoyama
Keita
K
Koizumi
Duo
D
Jin
Hong-Xiang
HX
Liu
Olga
O
Lopatina
Sarwat
S
Amina
Mohammad Saharul
MS
Islam
Jian-Jun
JJ
Huang
Mami
M
Noda
D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D009243:NAD; D036563:Cyclic ADP-Ribose; D010121:Oxytocin; D036541:ADP-ribosyl Cyclase