NAADP as a second messenger: neither CD38 nor base-exchange reaction are necessary for in vivo generation of NAADP in myometrial cells
- 1 January 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 292 (1), C227-C239
- https://doi.org/10.1152/ajpcell.00638.2005
Abstract
Nicotinic acid adenine dinucleotide phosphate (NAADP) has recently been shown to act as a second messenger controlling intracellular Ca2+responses in mammalian cells. Many questions remain regarding this signaling pathway, including the role of the ryanodine receptor (RyR) in NAADP-induced Ca2+transients. Furthermore, the exact metabolic pathway responsible for the synthesis of NAADP in vivo has not been determined. Here, we demonstrate that the NAADP mediated Ca2+release system is present in human myometrial cells. We also demonstrate that human myometrial cells use the NAADP second messenger system to generate intracellular Ca2+transients in response to histamine. It has been proposed in the past that the NAADP system in mammalian cells is dependent on the presence of functional RyRs. Here, we observed that the histamine-induced Ca2+transients are dependent on both the NAADP and inositol 1,4,5-trisphosphate signaling pathways but are independent of RyRs. The enzyme CD38 has been shown to catalyze the synthesis of NAADP in vitro by the base-exchange reaction. Furthermore, it has been proposed that this enzyme is responsible for the intracellular generation of NAADP in vivo. Using CD38 knockout mice, we observed that both the basal and histamine stimulated levels of NAADP are independent of CD38 and the base-exchange reaction. Our group is the first to demonstrate that NAADP is a second messenger for histamine-elicited Ca2+transients in human myometrial cells. Furthermore, the NAADP mediated mechanism in mammalian cells can be independent of RyRs and CD38. Our data provides novel insights into the understanding of the mechanism of action and metabolism of this new second messenger system.Keywords
This publication has 39 references indexed in Scilit:
- Regulation of intracellular levels of NAD: A novel role for CD38Biochemical and Biophysical Research Communications, 2006
- The Role of Cyclic-ADP-Ribose-Signaling Pathway in Oxytocin-Induced Ca2+ Transients in Human Myometrium CellsEndocrinology, 2004
- To be or not to be… Nicotinic acid adenine dinucleotide phosphate (NAADP): A new intracellular second messenger?Biological Research, 2004
- Nicotinic Acid Adenine Dinucleotide Phosphate Mediates Ca 2+ Signals and Contraction in Arterial Smooth Muscle via a Two-Pool MechanismCirculation Research, 2002
- CD38 is the major enzyme responsible for synthesis of nicotinic acid–adenine dinucleotide phosphate in mammalian tissuesBiochemical Journal, 2002
- The versatility and universality of calcium signallingNature Reviews Molecular Cell Biology, 2000
- Nicotinic acid adenine dinucleotide phosphate triggers Ca2+ release from brain microsomesCurrent Biology, 1999
- Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cellsNature, 1999
- ADP-ribosyl Cyclase and CD38 Catalyze the Synthesis of a Calcium-mobilizing Metabolite from NADP+Journal of Biological Chemistry, 1995
- Nicotinate Adenine Dinucleotide Phosphate (NAADP) Triggers a Specific Calcium Release System in Sea Urchin EggsPublished by Elsevier BV ,1995