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Vol. 285, Issue 2, 511-517, May 1998
Departments of
Biochemistry and Molecular Biology (A.E., D.P.) and
Pharmacology and Toxicology, College of Pharmacy (K.S., R.L.T.),
University of Georgia, Athens, Georgia
The contractile response to endothelin-1 (ET-1) appears to be modulated
by the relative density of ETA and ETB
receptors. To determine the effects of gender on the distribution of ET
receptors, we analyzed the endothelin receptor subtypes on membrane
fractions prepared from saphenous vein samples obtained from patients
of different genders undergoing coronary artery bypass graft surgery. The contractile response to ET-1 in the presence and absence of 1 µM
of the ETA receptor antagonist BQ-123 was also
investigated. Similar studies were repeated with endothelium-denuded
samples to study the role of endothelium- and smooth muscle-derived
ETB receptors. Competitive binding experiments were
performed on membrane fractions using [125I]ET-1 and
unlabeled ligands ET-1, ET-3, sarafatoxin 6c and BQ-123. Analysis of
the binding data with endothelium-intact samples yielded two classes of
binding sites in both women and men. In women, the maximum binding
capacities were 83 ± 6 and 97 ± 10 fmol/mg protein for
ETA and ETB receptors, respectively; the
corresponding values in men were 618 ± 121 and 201 ± 10 fmol/mg protein. In addition, ET-1-induced contractions were 2-fold
greater in men than in women at high ET-1 concentrations. Competitive
binding studies with endothelium-denuded saphenous veins demonstrated the presence of only ETA receptors in both female and male
tissue. These results indicate that the ratio and the density of ET
receptors are different in men and women, which might be an important
factor in the regulation of the contractile response.
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