Cyclosporine-Induced β-Adrenergic Receptor Down-Regulation in Bovine Pulmonary Artery Smooth Muscle Cells: A Pilot Study

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Abstract

We attempted to determine the effects of cyclosporine on β-adrenergic receptors in bovine pulmonary artery smooth muscle cells. Bovine pulmonary artery smooth muscle cells were exposed to cyclosporine at a concentration of 100 ng/ml in culture media for 5 days, and control bovine pulmonary artery smooth muscle cells were exposed to only culture media for the same 5-day period. β-Adrenergic receptors were measured as total binding capacity (Bmax) by nonlinear least squares fit of the specific binding curve. In a separate experiment β1- versus β2-adrenergic receptor subtypes were identified by computer modeling (LIGAND) of 17-19 point CGP20712A-125ICYP competition curves. Cyclosporine significantly (p=0.02) decreased bovine pulmonary artery smooth muscle β-adrenergic receptor density by 54% ± 7%. The Bmax for control versus treated cells was 38.9 ± 18 versus 17.7 ± 12 fmol/mg protein, respectively. Subtype determination of β-receptors revealed 70% or more β2- and 30% or less β1-adrenergic receptors. Cyclosporine caused a 54% reduction in overall β-adrenergic receptor density in bovine pulmonary artery smooth muscle cells. The reduction in Bmax is suspected not to be a result of selective down-regulation of β1-adrenergic receptors alone. We believe that cyclosporine may also contribute to a decrease in β2-adrenergic receptors.

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