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Cited by 433Calcium signaling and nucleotide metabolismAdenosine and Purinergic SignalingSirtuins and Resveratrol in Medicine

Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers

Lee, Hon Cheung·2001·Annual Review of Pharmacology and Toxicology
DOI 10.1146/annurev.pharmtox.41.1.317
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Abstract

Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The crystal structure of the cyclase has been solved and its active site identified. These two novel nucleotides have now been shown to be involved in a wide range of cellular functions including: cell cycle regulation in Euglena, a protist; gene expression in plants; and in animal systems, from fertilization to neurotransmitter release and long-term depression in brain. A battery of pharmacological reagents have been developed, providing valuable tools for elucidating the physiological functions of these two novel Ca(2+) messengers. This article reviews these recent results and explores the implications of the existence of multiple Ca(2+) messengers and Ca(2+) stores in cells.

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Crossref · 10.1146/annurev.pharmtox.41.1.317

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174 of 174 references verified0 citation errors · 0 not checkable

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  • CD38 possesses ADP-ribosyl cyclase activity that produces cyclic ADP-ribose (cADPR) from β-NAD+.

    “CD38 possesses ADP-ribosyl cyclase activity (Lee, 2001;Higashida et al., 2001a and2007;Boittin et al., 2003;Guse, 2005) that produces cyclic ADP-ribose (cADPR) from β-NAD + , also known as Vitamin B3, an abundant substrate in the brain (Denu, 2005).”

    From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Lee, 2001

  • cADPR mobilizes Ca2+ from intracellular stores, acting as a second messenger.

    “cADPR mobilizes Ca 2+ from intracellular Ca 2+ stores, thus acting as a second messenger (Lee, 2001).”

    From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Lee, 2001

  • CD38 is expressed in the brain and can catalyze the formation of cADPR from NAD+.

    “CD38 is expressed in the brain (Lee, 2001;Higashida et al., 2007) and can catalyze the formation of cyclic ADP-ribose (cADPR) from NAD + (Lee, 2001;Guse, 2005;Malvasi et al., 2008).”

    From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Lee, 2001

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Authors
Lee, H. C.
Affiliations
University of Minnesota (US)
Corresponding author
Lee, Hon Cheung
ORCID
Lee, Hon Cheung
Venue
Annual Review of Pharmacology and Toxicology
Publisher
Annual Reviews
Published
2001-04
Volume
41
Issue
1
Pages
317-345
ISSN
  • 0362-1642 (ISSN-L)
  • 1545-4304
DOI
10.1146/annurev.pharmtox.41.1.317
OpenAlex
W1895963467
Cited by
433
References
174
Citations by year
2026: 5 · 2025: 9 · 2024: 10 · 2023: 3 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 7 · 2014: 18 · 2013: 19 · 2012: 18
FWCI
3.01
Type
journal article
Language
en
Open access
closed
Locations
  • The Annual Review of Pharmacology and Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
  • National Institutes of Health (5r01gm060333-02, 5r01hd017484-18)
  • National Institute of General Medical Sciences (GM 60333, GM61568, R01GM061568)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD17484)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
cyclic ADP-ribose, NAADP, ADP-ribosyl cyclase, CD38, NAD+ metabolism, calcium signaling, intracellular calcium stores, cell cycle regulation, Euglena, plant gene expression, fertilisation (biology), neurotransmitter release, long-term depression
MeSH terms
Adenosine Diphosphate Ribose, Animals, Calcium, Humans, NADP, Calcium Signaling

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