title: Cyclic ADP-ribose requires CD38 to regulate the release of ATP in visceral smooth muscle.
abstract: It is well established that the intracellular second messenger cADP-ribose (cADPR) activates Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors. CD38 is a multifunctional enzyme involved in the formation of cADPR in mammals. CD38 has also been reported to transport cADPR in several cell lines. Here, we demonstrate a role for extracellular cADPR and CD38 in modulating the spontaneous, but not the electrical field stimulation-evoked, release of ATP in visceral smooth muscle. Using a small-volume superfusion assay and an HPLC technique with fluorescence detection, we measured the spontaneous and evoked release of ATP in bladder detrusor smooth muscles isolated from CD38(+/+) and CD38(-/-) mice. cADPR (1 nM) enhanced the spontaneous overflow of ATP in bladders isolated from CD38(+/+) mice. This effect was abolished by the inhibitor of cADPR receptors on sarcoplasmic reticulum 8-bromo-cADPR (80 μM) and by ryanodine (50 μm), but not by the nonselective P2 purinergic receptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonate (30 μM). cADPR failed to facilitate the spontaneous ATP overflow in bladders isolated from CD38(-/-) mice, indicating that CD38 is crucial for the enhancing effects of extracellular cADPR on spontaneous ATP release. Contractile responses to ATP were potentiated by cADPR, suggesting that the two adenine nucleotides may work in synergy to maintain the resting tone of the bladder. In conclusion, extracellular cADPR enhances the spontaneous release of ATP in the bladder by influx via CD38 and subsequent activation of intracellular cADPR receptors, probably causing an increase in intracellular Ca(2+) in neuronal cells.
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557-0575, USA.
authors: Leonie
authors: L
authors: Durnin
authors: Violeta N
authors: VN
authors: Mutafova-Yambolieva
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000819:agonists / Q000378:metabolism*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000378:metabolism; D006156:Guanosine Diphosphate Sugars / Q000378:metabolism; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D009243:NAD / Q000031:analogs & derivatives / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D001743:Urinary Bladder
chemical_list: C493642:8-bromo-cyclic-ADP-ribose; D004791:Enzyme Inhibitors; D006150:Guanine Nucleotides; D006156:Guanosine Diphosphate Sugars; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C067025:cyclic ADP-ribose receptor; C090657:cyclic guanosine diphosphate-ribose; D009243:NAD; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; C102728:nicotinamide guanine dinucleotide; D000255:Adenosine Triphosphate; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D000252:Calcium-Transporting ATPases