Novel localization of CD38 in perivascular sympathetic nerve terminals.
Using high performance liquid chromatography fraction analysis we have recently established that numerous smooth muscle preparations, including the canine mesenteric artery and vein, release beta-nicotinamide adenine dinucleotide upon short-pulse electrical field stimulation in tetrodotoxin- and omega-conotoxin GVIA-sensitive manners [ Release of beta-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder. J Biol Chem 279:48893-48903.]. The beta-nicotinamide adenine dinucleotide metabolites ADP-ribose and cyclic ADP-ribose are also present in the tissue superfusates. CD38 is a multifunctional enzyme involved in the degradation of beta-nicotinamide adenine dinucleotide to ADP-ribose and cyclic ADP-ribose. Western immunoblot analysis revealed that CD38 is expressed in both artery and vein. Confocal laser scanning microscopy established colocalization of CD38 with tyrosine hydroxylase, synaptotagmin and synaptic vesicle protein in both blood vessels. High performance liquid chromatography with fluorescence detection demonstrated that whole tissue segments metabolize 1,N(6)-etheno-nicotinamide adenine dinucleotide to 1,N(6)-etheno-ADP-ribose and nicotinamide-guanine dinucleotide to cyclic GDP-ribose, suggesting the presence of both nicotinamide adenine dinucleotide-glycohydrolase and ADP-ribosyl cyclase activities in these blood vessels. Both enzymes appear to be associated with the membrane fraction, and therefore might be attributed to CD38. These data demonstrate a previously uncharacterized localization of CD38 in perivascular autonomic nerve terminals. Therefore, the beta-nicotinamide adenine dinucleotide/CD38 system may provide new mechanisms in autonomic neurovascular control.
Department of Physiology and Cell Biology, Anderson Medical Sciences Building/MS 352, University of Nevada School of Medicine, Reno, NV 89557-0271, USA.
L M
LM
Smyth
L T
LT
Breen
I A
IA
Yamboliev
V N
VN
Mutafova-Yambolieva
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology*; D006150:Guanine Nucleotides / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009243:NAD / Q000031:analogs & derivatives / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D006150:Guanine Nucleotides; D009419:Nerve Tissue Proteins; D009243:NAD; C102728:nicotinamide guanine dinucleotide; D014446:Tyrosine 3-Monooxygenase; D051997:ADP-ribosyl Cyclase 1