TY - JOUR
T1 - Extracellular cyclic ADP-ribose potentiates ACh-induced contraction in bovine tracheal smooth muscle
AU - Franco, Luisa
AU - Bruzzone, Santina
AU - Song, Pinfang
AU - Guida, Lucrezia
AU - Zocchi, Elena
AU - Walseth, Timothy F.
AU - Crimi, Emanuele
AU - Usai, Cesare
AU - De Flora, Antonio
AU - Brusasco, Vito
PY - 2001/1
Y1 - 2001/1
N2 - Cyclic ADP-ribose (cADPR), a universal calcium releaser, is generated from NAD+ by an ADP-ribosyl cyclase and is degraded to ADP-ribose by a cADPR hydrolase. In mammals, both activities are expressed as ectoenzymes by the transmembrane glycoprotein CD38. CD38 was identified in both epithelial cells and smooth myocytes isolated from bovine trachea. Intact tracheal smooth myocytes (TSMs) responded to extracellular cADPR (100 μM) with an increase in intracellular calcium concentration ([Ca2+]i) both at baseline and after acetylcholine (ACh) stimulation. The nonhydrolyzable analog 3-deaza-cADPR (10 nM) elicited the same effects as cADPR, whereas the cADPR antagonist 8-NH2-cADPR (10 μM) inhibited both basal and ACh-stimulated [Ca2+]i levels. Extracellular cADPR or 3-deaza-cADPR caused a significant increase of ACh-induced contraction in tracheal smooth muscle strips, whereas 8-NH2-cADPR decreased it. Tracheal mucosa strips, by releasing NAD+, enhanced [Ca2+]i in isolated TSMs, and this increase was abrogated by either NAD+-ase or 8-NH2-cADPR. These data suggest the existence of a paracrine mechanism whereby mucosa-released extracellular NAD+ plays a hormonelike function and cADPR behaves as second messenger regulating calcium-related contractility in TSMs.
AB - Cyclic ADP-ribose (cADPR), a universal calcium releaser, is generated from NAD+ by an ADP-ribosyl cyclase and is degraded to ADP-ribose by a cADPR hydrolase. In mammals, both activities are expressed as ectoenzymes by the transmembrane glycoprotein CD38. CD38 was identified in both epithelial cells and smooth myocytes isolated from bovine trachea. Intact tracheal smooth myocytes (TSMs) responded to extracellular cADPR (100 μM) with an increase in intracellular calcium concentration ([Ca2+]i) both at baseline and after acetylcholine (ACh) stimulation. The nonhydrolyzable analog 3-deaza-cADPR (10 nM) elicited the same effects as cADPR, whereas the cADPR antagonist 8-NH2-cADPR (10 μM) inhibited both basal and ACh-stimulated [Ca2+]i levels. Extracellular cADPR or 3-deaza-cADPR caused a significant increase of ACh-induced contraction in tracheal smooth muscle strips, whereas 8-NH2-cADPR decreased it. Tracheal mucosa strips, by releasing NAD+, enhanced [Ca2+]i in isolated TSMs, and this increase was abrogated by either NAD+-ase or 8-NH2-cADPR. These data suggest the existence of a paracrine mechanism whereby mucosa-released extracellular NAD+ plays a hormonelike function and cADPR behaves as second messenger regulating calcium-related contractility in TSMs.
KW - Acetylcholine
KW - Adenosine 5′-diphosphate-ribosyl cyclase
KW - CD38
KW - Calcium-related contraction of tracheal strips
KW - Cyclic adenosine 5′-diphosphate-ribose hydrolase
KW - Nicotinamide adenine dinucleotide/cyclic adenosine 5′-diphosphate-ribose-mediated paracrine mechanisms
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U2 - 10.1152/ajplung.2001.280.1.l98
DO - 10.1152/ajplung.2001.280.1.l98
M3 - Article
C2 - 11133499
AN - SCOPUS:0034997420
SN - 1040-0605
VL - 280
SP - L98-L106
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 1 24-1
ER -