CD38 gene disruption inhibits the contraction induced by alpha-adrenoceptor stimulation in mouse aorta.
CD38 is an ectoenzyme with ADP-ribosyl cyclase and hydrolase activities, which synthesizes cyclic ADP-ribose from NAD and hydrolyzes cyclic ADP-ribose to ADP-ribose. It has been shown that cyclic ADP-ribose is a potent Ca(2+) mobilizing messenger in many cells. To know the physiological role of cyclic ADP-ribose in vascular smooth muscle, we examined the effects of various agonists in the aorta isolated from CD38 knockout (CD38(-/-)) mouse. Western blot analysis showed that CD38 protein was detected in the aorta isolated from wild-type (CD38(+/+)) mouse, but not from CD38(-/-) mouse. In the aortae isolated from both CD38(+/+) and CD38(-/-) mice, KCl, phenylephrine and norepinephrine induced concentration-dependent contraction. KCl produced similar concentration-dependent responses in the aortae from both CD38(+/+) and CD38(-/-) mice. Maximum force of contraction induced by KCl (65 mM) was same in the size. Phenylephrine- and norepinephrine-induced contractions were, however, significantly smaller in the aortae from CD38(-/-) mice than in those from CD38(+/+) mice. 5-Hydroxytryptamine, endothelin-1, caffeine and thapsigargin-induced contractions were not significantly different in these two aortae. These results suggest that CD38 gene disruption inhibits alpha-adrenoceptor-induced vascular contractions and cyclic ADP-ribose-mediated signal transduction system is committed in these responses.
Mitsui-Saito
Minori
M
Department of Molecular Pharmacology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Kato
Ichiro
I
Takasawa
Shin
S
Okamoto
Hiroshi
H
Yanagisawa
Teruyuki
T
D036541:ADP-ribosyl Cyclase / Q000172:deficiency* / Q000235:genetics*; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology; D017353:Gene Deletion; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D015703:Antigens, CD; D019332:Endothelin-1; D008562:Membrane Glycoproteins; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1