TY - JOUR
T1 - NAADP as a second messenger
T2 - Neither CD38 nor base-exchange reaction are necessary for in vivo generation of NAADP in myometrial cells
AU - Soares, Sandra
AU - Thompson, Michael
AU - White, Thomas
AU - Isbell, Amir
AU - Yamasaki, Michiko
AU - Prakash, Yodeta
AU - Lund, Frances E.
AU - Galione, Antony
AU - Chini, Eduardo N.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Base-exchange reaction
KW - CD38
KW - Endoplasmic reticulum
KW - Inositol 1,4,5-trisphosphate
KW - Nicotinic acid adenine dinucleotide phosphate
KW - Ryanodine channel
KW - cADP ribose
UR - http://www.scopus.com/inward/record.url?scp=33846276537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846276537&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00638.2005
DO - 10.1152/ajpcell.00638.2005
M3 - Article
C2 - 16790499
AN - SCOPUS:33846276537
SN - 0363-6143
VL - 292
SP - C227-C239
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 1
ER -