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

Mitsui-Saito, Minori; Kato, Ichiro; Takasawa, Shin; Okamoto, Hiroshi; Yanagisawa, Teruyuki

doi:10.1292/jvms.65.1325

Cited by 25 publications

(17 citation statements)

References 28 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The previously reported literature has suggested that ADPR cyclase contributes to agonistinduced vasoconstriction. ADPR cyclase, cADPR, and RyRs participate in ANG II-mediated increases in [Ca 2ϩ ] i in preglomerular resistance arterioles (19); those triggered by KClinduced depolarization (17) and constrictor responses to NE are attenuated in aortic rings of CD38Ϫ/Ϫ mice (39). RyRs also have been implicated in NE signaling in vascular myocytes (8).…”

Section: Discussionmentioning

confidence: 99%

ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo

Thai

Fellner²,

Arendshorst

2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

An important role for the enzyme ADP-ribosyl cyclase (ADPR cyclase) and its downstream targets, the ryanodine receptors (RyR), is emerging for a variety of vascular systems. We hypothesized that the ADPR cyclase/RyR pathway contributes to regulation of renal vasomotor tone in vivo. To test this, we continuously measured renal blood flow (RBF) in anesthetized Sprague-Dawley rats. Infusion of the ADPR cyclase inhibitor nicotinamide intrarenally at low doses inhibits angiotensin II (ANG II)- and norepinephrine (NE)-induced vasoconstriction by 72 and 67%, respectively (P < 0.001). RBF studies in rats were extended to mice lacking the predominant form of ADPR cyclase (CD38). Acute renal vasoconstrictor responses to ANG II and NE are impaired by 59 and 52%, respectively, in anesthetized CD38-/- mice compared with wild-type controls (P < 0.05). Intrarenal injection of the RyR activator FK506 decreases RBF by 22% (P > 0.03). Furthermore, RyR inhibition with ruthenium red attenuates ANG II and NE responses by 50 and 59%, respectively (P < or = 0.01). Given at higher doses, nicotinamide increases basal RBF by 22% (P > 0.001). Non-receptor-mediated renal vasoconstriction by L-type voltage-gated Ca(2+) channels is also dependent on ADPR cyclase and RyRs. Nicotinamide and ruthenium red inhibit constriction by the L-type channel agonist BAY K 8644 by 59% (P > 0.02) and 63% (P > 0.001). We conclude that 1) ADPR cyclase activity contributes to regulation of renal vasomotor tone under resting conditions, 2) renal vasoconstriction induced by G protein-coupled receptor agonists ANG II and NE is mediated in part by ADPR cyclase and RyRs, and 3) ADPR cyclase and RyRs participate in L-type channel-mediated renal vasoconstriction in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo

Thai

Fellner²,

Arendshorst

2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…The mice also manifest multiple defects relating to Ca 2+ signaling, including that of insulin secretion [97], hormonal signaling in pancreatic acinar cells [98], migration of dendritic cell precursors [99], bone resorption [100], airway responsiveness [101], α-adrenoceptor signaling in aorta [102], cardiac hypertrophy [103], susceptibility to bacterial infection [55], as well as social behavior in mice through modulation of oxytocin secretion [66]. In humans, the deletion of the CD38 gene may well be lethal since no CD38-negative individual has yet been identified in a large screen [104].…”

Section: Enzymatic Synthesis Of Cadpr By Cd38mentioning

confidence: 99%

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Lee

2011

Sci. China Life Sci.

View full text Add to dashboard Cite

The concept advanced by Berridge and colleagues that intracellular Ca 2+ -stores can be mobilized in an agonist-dependent and messenger (IP 3 )-mediated manner has put Ca 2+ -mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca 2+ -stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP 3 ) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.cyclic ADP-ribose, cADPR, NAADP, nicotinic acid adenine dinucleotide phosphate, CD38, ADP-ribosyl cyclase, Calcium mobilization and signaling Citation:Lee H C. Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. Sci China Life Sci, 2011Sci, , 54: 699 -711, doi: 10.1007 In 1983, Berridge and colleagues published a study showing that agonists, such as carbachol, can activate Ca 2+ release from non-mitochondrial Ca 2+ stores and the effect is mediated by a Ca 2+ messenger, inositol 1,4,5-trisphosphate (IP 3 ) [1]. The targeted Ca 2+ stores were later identified as the endoplasmic reticulum (ER), which has since been shown to be the major intracellular Ca 2+ stores. This seminal study ushered in the current field of Ca 2+ signaling as we know it and has made the field center stage. IP 3 is derived from a phospholipid, phosphatidyl inositol 4,5-bisphosphate, present on the cytoplasmic side of the plasma membrane. Agonist binding to its specific receptor leads to activation of phospholipase C and the hydrolysis of the phospholipid, releasing the head group that is IP 3 . The structure of IP 3 is shown in Figure 1. It has three phosphates on the inositol ring. Both the number of phosphates and the position of the phosphates are critical to the binding of IP 3 to its receptor in the ER. The space-filling model of IP 3 shown in Figu...

show abstract

“…CD38-generated cADPR plays a critical role in Ca 2ϩ -induced insulin secretion (21), osteoclast-mediated bone resorption (35), vasoconstriction (27), myometrium function (9), and immune function (28,29). Using these mice, we have previously demonstrated that CD38 is the main source of cADPR in the lungs.…”

mentioning

confidence: 99%

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

Guedes¹,

Paulin²,

Rivero-Nava³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

-The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 g of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (RL) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced R L were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists. interleukin-13; inflammation; asthma; eosinophil; airway smooth muscle CD38 IS A MULTIFUNCTIONAL ECTOENZYME that catalyzes the conversion of ␤-nicotinamide adenine dinucleotide to cyclic ADP-ribose (cADPR) and ADP-ribose (16). Both CD38 and its product cADPR are present in airway smooth muscle (ASM) cells and other mammalian cell types (8,26,32,39). Together with inositol 1,4,5-trisphosphate, cADPR is an important mediator of intracellular calcium ([Ca 2ϩ ] i ) release in smooth muscle cells including that of the airways (7,20,31). The dynamics of [Ca 2ϩ ] i responses to stimuli are central in the regulation of ASM contraction, bronchomotor tone, and airway caliber (33). cADPR induces Ca 2ϩ release from the sarcoplasmic reticulum through activation of ryanodine receptor channels in ASM cells (31). The [Ca 2ϩ ] i responses of human ASM cells exposed to acetylcholine, thrombin, and bradykinin are reduced by the competitive cADPR antagonist 8-bromo-cADPR in a magnitude that correlates positively with the level of CD38 expression (6).CD38-deficient (CD38KO) mice have been used to elucidate the role of CD38 in the function of several organs. CD38-generated cADPR plays a critical role in Ca 2ϩ -induced insulin secretion (21), os...

show abstract

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

Cited by 25 publications

References 28 publications

ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo

ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

Contact Info

Product

Resources

About