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(Circulation. 2000;102:2548.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Isolation and Characterization of Coenzyme A Glutathione Disulfide as a Parathyroid-Derived Vasoconstrictive Factor

Joachim Jankowski, PhD; Anna Schröter; Martin Tepel, MD; Markus van der Giet, MD; Nina Stephan, MSc; Jiankai Luo, MD; Walter Zidek, MD; Hartmut Schlüter, PhD

From the Medizinische Klinik I, Universitäts-Klinik Marienhospital, Ruhr University of Bochum, Germany.

Correspondence to PD Dr H. Schlüter, Universitäts-Klinik Marienhospital der Ruhr-Universität Bochum, Hölkeskampring 40, 44625 Herne, Germany. E-mail hartmut.schlueter{at}ruhr-uni-bochum.de

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.

Methods and 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 [³H]thymidine method, is characterized by a threshold of 10^-8 mol/L and a maximum effect of 10 µmol/L, increasing VSMC proliferation 254±21% above control. A dose of 10 µmol/L methylmalonyl-CoA and 10 µmol/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 µmol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 µmol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 µmol/L) (48% compared with CoA-SSG without antagonist; each P<0.05 versus control), indicating that the effect is mediated partly via A₂ and partly via P₂Y₁ and/or P₂Y₄ 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.

Key Words: enzymes • muscle, smooth • cells