This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Yang, L. Articles by Sonner, J. M. Search for Related Content PubMed PubMed Citation Articles by Yang, L. Articles by Sonner, J. M. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

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

Liya Yang, PhD^*, Pavle S. Milutinovic, MS^*, Robert J. Brosnan, DVM, PhD, Edmond I. Eger, II, MD^*, and James M. Sonner, MD^*

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; and The Department of Surgical and Radiological Sciences, University of California, School of Veterinary Medicine, Davis, California.

Address correspondence to Sonner, MD, Department of Anesthesia, Room S-455i, Box 0464, 513 Parnassus Ave., University of California, San Francisco, CA 94143-0464. Address e-mail to sonnerj{at}anesthesia.ucsf.edu.

INTRODUCTION: 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 -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.

METHODS: ₁ß₂ GABA_A and 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.

RESULTS: 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 ₁ß₂ 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.

CONCLUSIONS: 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.

This article has been cited by other articles:

				Y. Weng, T. T. Hsu, J. Zhao, S. Nishimura, G. G. Fuller, and J. M. Sonner Isovaleric, Methylmalonic, and Propionic Acid Decrease Anesthetic EC50 in Tadpoles, Modulate Glycine Receptor Function, and Interact with the Lipid 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine Anesth. Analg., May 1, 2009; 108(5): 1538 - 1545. [Abstract] [Full Text] [PDF]

				R. J. Brosnan and T. L. Pham Carbon dioxide negatively modulates N-methyl-D-aspartate receptors Br. J. Anaesth., November 1, 2008; 101(5): 673 - 679. [Abstract] [Full Text] [PDF]

				L. Yang and J. M. Sonner The Anesthetic-Like Effects of Diverse Compounds on Wild-Type and Mutant {gamma}-Aminobutyric Acid Type A and Glycine Receptors Anesth. Analg., March 1, 2008; 106(3): 838 - 845. [Abstract] [Full Text] [PDF]