CD38 Gene Disruption Inhibits the Contraction Induced by α-Adrenoceptor Stimulation in Mouse Aorta

Abstract

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 Ca²⁺ 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 α-adrenoceptor-induced vascular contractions and cyclic ADP-ribose-mediated signal transduction system is committed in these responses.