The Plasticizer Di(2-ethylhexyl) Phthalate Modulates γ-Aminobutyric Acid Type A and Glycine Receptor Function

Abstract

Intravenous (IV) fluid bags made of polyvinyl chloride (PVC) often contain the plasticizer di(2-ethylhexyl) phthalate (DEHP) to make the PVC flexible. Phthalate esters have been reported to inhibit neuronal nicotinic acetylcholine receptors, which are sensitive to many inhaled anesthetics. This raises the possibility that DEHP might modulate the function of other cys-loop receptors, such as gamma-amino butyric acid type A (GABA(A)) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors. alpha(1)beta(2) GABA(A) and alpha(1) glycine receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. We then measured the effect of buffers from IV bags containing DEHP-plasticized PVC, and of buffers saturated with DEHP, on agonist-induced currents. Agonist-induced currents from glycine receptors were enhanced by buffers from IV bags containing DEHP-plasticized PVC by 291.9% +/- 84.5% (mean +/- se) and from saturated solutions of DEHP by 70.8% +/- 16.7%. Agonist-induced currents from alpha(1)beta(2) GABA(A) receptors were inhibited by buffers from IV bags containing DEHP-plasticized PVC by 19.3% +/- 3.2% and by 31.7% +/- 7.0% from buffers saturated with DEHP. The plasticizer DEHP modulates the function of both GABA(A) and glycine receptors. DEHP contamination can confound the results of electrophysiologic studies of anesthetic mechanisms on these receptors if DEHP-plasticized PVC is present in the experimental apparatus.