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. Th e identification of CoA-SSG in human parathyroid glands and its action on c ultured vascular smooth muscle cells (VSMCs) are described here. Methods and Results-After purification to homogeneity by several chromatogr aphic steps, CoA-SSG was identified by matrix-assisted laser desorption/ion ization mass spectrometry and enzymatic analysis. The dose-dependent growth -stimulating effect of CoA-SSG on VSMCs, measured by the [H-3]thymidine met hod, is characterized by a threshold of 10(-8) mol/L and a maximum effect o f 10 mu mol/L, increasing VSMC proliferation 254+/-21% above control. A dos e of 10 mu mol/L methylmalonyl-CoA and 10 mu mol/L CoA increased the rate o f proliferation of VSMCs only by 178+/-43% and 50+/-42% above control. resp ectively. Glutathione has no proliferative effect on VSMCs. The growth-stim ulating effect of CoA-SSG (1 mu mol/L) was decreased by the antagonists 3,7 -dimethyl-1-propargylxanthine (DMPX; 11 mu mol/L) (38% compared with CoA-SS G without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic ac id (PPADS; 10 mu mol/L) (48% compared with CoA-SSG without antagonist; each P<0.05 versus control), indicating that the effect is mediated partly via A, and partly via P2Y1 and/or P2Y4 receptor. Conclusions-CoA-SSG may play a regulatory role in VSMC growth as a progress ion factor and thereby could play an important role in development of hyper tension.