The plasticizer di(2-ethylhexyl) phthalate modulates γ-aminobutyric acid type A and glycine receptor function

Liya Yang, Pavle S. Milutinovic, Robert J Brosnan, Edmond I. Eger, James M. Sonner

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 γ-amino butyric acid type A (GABAA) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors. METHODS: α1β2 GABAA and α1 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 α1β2 GABAA 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 GABAA 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.

Original languageEnglish (US)
Pages (from-to)393-396
Number of pages4
JournalAnesthesia and Analgesia
Volume105
Issue number2
DOIs
StatePublished - Aug 2007

Fingerprint

Aminobutyrates
Glycine Receptors
Plasticizers
Polyvinyl Chloride
Buffers
GABA-A Receptors
Anesthetics
phthalic acid
Cysteine Loop Ligand-Gated Ion Channel Receptors
Butyric Acid
Xenopus laevis
Nicotinic Receptors
Constriction
Oocytes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The plasticizer di(2-ethylhexyl) phthalate modulates γ-aminobutyric acid type A and glycine receptor function. / Yang, Liya; Milutinovic, Pavle S.; Brosnan, Robert J; Eger, Edmond I.; Sonner, James M.

In: Anesthesia and Analgesia, Vol. 105, No. 2, 08.2007, p. 393-396.

Research output: Contribution to journalArticle

Yang, Liya ; Milutinovic, Pavle S. ; Brosnan, Robert J ; Eger, Edmond I. ; Sonner, James M. / The plasticizer di(2-ethylhexyl) phthalate modulates γ-aminobutyric acid type A and glycine receptor function. In: Anesthesia and Analgesia. 2007 ; Vol. 105, No. 2. pp. 393-396.
@article{04c19b1604a243f8991509e91608fd93,
title = "The plasticizer di(2-ethylhexyl) phthalate modulates γ-aminobutyric acid type A and glycine receptor function",
abstract = "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 γ-amino butyric acid type A (GABAA) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors. METHODS: α1β2 GABAA and α1 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 α1β2 GABAA 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 GABAA 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.",
author = "Liya Yang and Milutinovic, {Pavle S.} and Brosnan, {Robert J} and Eger, {Edmond I.} and Sonner, {James M.}",
year = "2007",
month = "8",
doi = "10.1213/01.ane.0000267336.37735.d7",
language = "English (US)",
volume = "105",
pages = "393--396",
journal = "Anesthesia and Analgesia",
issn = "0003-2999",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - The plasticizer di(2-ethylhexyl) phthalate modulates γ-aminobutyric acid type A and glycine receptor function

AU - Yang, Liya

AU - Milutinovic, Pavle S.

AU - Brosnan, Robert J

AU - Eger, Edmond I.

AU - Sonner, James M.

PY - 2007/8

Y1 - 2007/8

N2 - 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 γ-amino butyric acid type A (GABAA) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors. METHODS: α1β2 GABAA and α1 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 α1β2 GABAA 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 GABAA 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.

AB - 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 γ-amino butyric acid type A (GABAA) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors. METHODS: α1β2 GABAA and α1 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 α1β2 GABAA 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 GABAA 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.

UR - http://www.scopus.com/inward/record.url?scp=34547574253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547574253&partnerID=8YFLogxK

U2 - 10.1213/01.ane.0000267336.37735.d7

DO - 10.1213/01.ane.0000267336.37735.d7

M3 - Article

C2 - 17646496

AN - SCOPUS:34547574253

VL - 105

SP - 393

EP - 396

JO - Anesthesia and Analgesia

JF - Anesthesia and Analgesia

SN - 0003-2999

IS - 2

ER -