The effect of the plasticizers TBEP (tris-(2-butoxyethyl)-phosphate) and DEHP (di-(2-ethylhexyl)-phthalate) on beta-adrenergic ligand binding to alpha 1-acid glycoprotein and mononuclear leukocytes.

G Sager, C Little

Index: Biochem. Pharmacol. 38(15) , 2551-7, (1989)

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Abstract

The plasticizers tris-(2-butoxyethyl)-phosphate (TBEP) and di-(2-ethylhexyl)-phthalate (DEHP) and the beta-adrenergic receptor-blockers [3H]-(-)-dihydroalprenolol ([3H]-(-)-DHA) and [3H]-(-)-CGP 12177 were tested for their ability to interact with beta-adrenergic binding to alpha 1-acid glycoprotein (AAG) and mononuclear leukocytes (MNL). The IC50-values, obtained by displacement of [3H]-(-)-DHA bound to AAG, were 3.5 nM, 2 microM and 4 microM for TBEP, (-)-alprenolol and DEHP, respectively. (+/-)-CGP 12177 had virtually no effect on radioligand binding to AAG. The [3H]-(-)-CGP 12177 binding to MNL consisted of beta-adrenergic receptor binding (Kd = 210 pM) and non-saturable binding. [3H]-(-)-DHA was bound to two different classes of binding sites on MNL, the beta-adrenergic receptors (Kd = 440 pM) and a secondary class of binding sites (Kd = 64 nM). (+/-)-CGP 12177 displaced about 30% of [3H]-(-)-DHA from MNL with an IC50-value of 190 pm. (-)-ALP displaced about 85% of total bound radioligand and gave a biphasic displacement curve with IC50-values of 320 pM and 690 mM, respectively. TBEP displaced a considerable fraction of [3H]-(-)-CGP 12177 and [3H]-(-)-DHA bound to MNL beta-adrenergic receptors, whereas DEHP had no effect. In contrast, DEHP caused displacement of [3H]-(-)-DHA from the MNL low affinity sites, but was a markedly less potent displacer compared to TBEP. The present study shows that TBEP and DEHP interact with beta-adrenergic transport proteins, non-specific tissue binding sites and beta-adrenergic receptors coupled to adenylate cyclase. Plasticizers may thus affect the biology and pharmacology of the beta-adrenergic signal system.