Extracellular cyclic ADP-ribose potentiates ACh-induced contraction in bovine tracheal smooth muscle.
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 microM) with an increase in intracellular calcium concentration ([Ca(2+)](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-NH(2)-cADPR (10 microM) inhibited both basal and ACh-stimulated [Ca(2+)](i) levels. Extracellular cADPR or 3-deaza-cADPR caused a significant increase of ACh-induced contraction in tracheal smooth muscle strips, whereas 8-NH(2)-cADPR decreased it. Tracheal mucosa strips, by releasing NAD(+), enhanced [Ca(2+)](i) in isolated TSMs, and this increase was abrogated by either NAD(+)-ase or 8-NH(2)-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.
Franco
L
L
Biocrystallography Centre-Consiglio Nazionale delle Ricerche, University Federico II, 80134 Naples, Italy.
Bruzzone
S
S
Song
P
P
Guida
L
L
Zocchi
E
E
Walseth
T F
TF
Crimi
E
E
Usai
C
C
De Flora
A
A
Brusasco
V
V
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives*; D005110:Extracellular Space / Q000201:enzymology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000201:enzymology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000032:analysis; D019899:Paracrine Communication / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology; D020545:Respiratory Mucosa / Q000737:chemistry / Q000201:enzymology; D014132:Trachea / Q000166:cytology / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D014665:Vasodilator Agents; C402294:cyclic 3-deazaadenosine diphosphoribose; D009243:NAD; D036563:Cyclic ADP-Ribose; C082175:8-aminoadenosine cyclic 3',5'-(hydrogen phosphate) 5'-ribofuranosyl ester; D000246:Adenosine Diphosphate Ribose; C090939:GDP-ribosyl cyclase; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D002118:Calcium