Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor.
BACKGROUND
Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and its action on cultured vascular smooth muscle cells (VSMCs) are described here.


RESULTS
After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the [(3)H]thymidine method, is characterized by a threshold of 10(-)(8) mol/L and a maximum effect of 10 micromol/L, increasing VSMC proliferation 254+/-21% above control. A dose of 10 micromol/L methylmalonyl-CoA and 10 micromol/L CoA increased the rate of proliferation of VSMCs only by 178+/-43% and 50+/-42% above control, respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 micromol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 micromol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 micromol/L) (48% compared with CoA-SSG without antagonist; each P:<0. 05 versus control), indicating that the effect is mediated partly via A(2) and partly via P(2)Y(1) and/or P(2)Y(4) receptor.


CONCLUSIONS
CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension.
Jankowski
J
J
Medizinische Klinik I, Universitäts-Klinik Marienhospital, Ruhr University of Bochum, Germany.
Schröter
A
A
Tepel
M
M
van der Giet
M
M
Stephan
N
N
Luo
J
J
Zidek
W
W
Schlüter
H
H
D000085:Acetates / Q000737:chemistry; D000804:Angiotensin II / Q000819:agonists; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003065:Coenzyme A / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008623:Mercaptoethanol / Q000737:chemistry; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010280:Parathyroid Glands / Q000737:chemistry* / Q000201:enzymology*; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D000085:Acetates; D004220:Disulfides; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; C057837:3,7-dimethyl-1-propargylxanthine; D008623:Mercaptoethanol; C019305:coenzyme A-glutathione mixed disulfide; D005978:Glutathione; D013805:Theobromine; D003065:Coenzyme A