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  • Title: Beta adrenergic antagonists inhibit serotonin uptake by pulmonary vascular cells in culture.
    Author: Lee SL, Fanburg BL.
    Journal: J Pharmacol Exp Ther; 1991 May; 257(2):895-900. PubMed ID: 1674537.
    Abstract:
    Beta adrenergic antagonists have been demonstrated to show stereoselective affinity for serotonin (5-HT) receptors in the central nervous system, and competitively inhibit 5-HT transport of platelets, but have not previously been evaluated for their influence on either 5-HT receptors or 5-HT transport systems of vascular cells. We have reported stimulation of 5-HT uptake by subjection of endothelial (EC) and smooth muscle cells (SMC) to anoxia. We now report that (+/-)-propranolol inhibits 5-HT uptake by both room air- and anoxia-exposed EC and SMC in culture. The effect on SMC was more marked than that on EC and showed a similar inhibition as ketanserin. The relative inhibitory potencies of beta adrenergic antagonists and ketanserin on uptake of 5-HT by SMC were as follows: (+/-)-propranolol = ketanserin greater than alprenolol = pindolol greater than oxprenolol = atenolol. The beta adrenergic receptor agonist, isoproterenol, in the presence of isobutylmethylxanthine, an inhibitor of phosphodiesterase, produced a high elevation of cyclic AMP in SMC along with a cellular configurational change and partially inhibited uptake of 5-HT. Propranolol inhibited 5-HT uptake both in the presence and absence of isoproterenol plus isobutylmethylxanthine, suggesting that its inhibitory effect was not mediated through its interaction at the beta adrenergic receptor. Kinetic analyses of the effect of propranolol on 5-HT uptake indicated that propranolol reduced 5-HT uptake by noncompetitive inhibition. We conclude that beta adrenergic antagonists block vascular cell uptake of 5-HT through an action other than interaction with the beta adrenergic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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