scholarly journals Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake

2014 ◽  
Vol 85 (5) ◽  
pp. 747-757 ◽  
Author(s):  
Malav Trivedi ◽  
Jayni Shah ◽  
Nathaniel Hodgson ◽  
Hyang-Min Byun ◽  
Richard Deth
Keyword(s):  
Dna Methylation ◽  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporter ◽  
Global Dna Methylation ◽  
Excitatory Amino Acid Transporter ◽  
Acid Transporter ◽  
Type 3 ◽  
Cysteine Uptake

Effects of Volatile Anesthetics on Glutamate Transporter, Excitatory Amino Acid Transporter Type 3

2002 ◽  
Vol 96 (6) ◽  
pp. 1492-1497 ◽  
Author(s):  
Sang-Hwan Do ◽  
Ganesan L. Kamatchi ◽  
Jacqueline M. Washington ◽  
Zhiyi Zuo
Keyword(s):  
Protein Kinase C ◽  
Amino Acid ◽  
Protein Kinase ◽  
Excitatory Amino Acid ◽  
Volatile Anesthetics ◽  
Amino Acid Transporter ◽  
Excitatory Amino Acid Transporter ◽  
Kinase C ◽  
Acid Transporter ◽  
Type 3

Background Glutamate transporters play an important role in maintaining extracellular glutamate homeostasis. The authors studied the effects of volatile anesthetics on one type of glutamate transporters, excitatory amino acid transporter type 3 (EAAT3), and the role of protein kinase C in mediating these effects. Methods Excitatory amino acid transporter type 3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. Using two-electrode voltage clamp, membrane currents were recorded before, during, and after application of L-glutamate. Responses were quantified by integrating the current trace and are reported as microcoulombs. Data are mean +/- SEM. Results L-Glutamate-induced responses were increased gradually with the increased concentrations of isoflurane, a volatile anesthetic. At 0.52 and 0.70 mm isoflurane, the inward current was significantly increased compared with control. Isoflurane (0.70 mm) significantly increased Vmax (maximum velocity) (3.6 +/- 0.4 to 5.1 +/- 0.4 microC; P < 0.05) but not Km (Michoelis-Menten Constant) (55.4 +/- 17.0 vs. 61.7 +/- 13.6 microm; P > 0.05) of EAAT3 for glutamate compared with control. Treatment of the oocytes with phorbol-12-myrisate-13-acetate, a protein kinase C activator, caused a significant increase in transporter current (1.7 +/- 0.2 to 2.5 +/- 0.2 microC; P < 0.05). Responses in the presence of the combination of phorbol-12-myrisate-13-acetate and volatile anesthetics (isoflurane, halothane, or sevoflurane) were not greater than those when volatile anesthetic was present alone. Oocytes pretreated with any of the three protein kinase C inhibitors alone (chelerythrine, staurosporine, or calphostin C) did not affect basal transporter current. Although chelerythrine did not change the anesthetic effects on the activity of EAAT3, staurosporine or calphostin C abolished the anesthetic-induced increase of EAAT3 activity. Conclusions These data suggest that volatile anesthetics enhance EAAT3 activity and that protein kinase C is involved in mediating these anesthetic effects.

scholarly journals Aminophylline and Ephedrine, but Not Flumazenil, Inhibit the Activity of the Excitatory Amino Acid Transporter 3 Expressed in Xenopus Oocytes and Reverse the Increased Activity by Propofol

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Sohyeon Moon ◽  
Hee Jung Baik
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporter ◽  
Pi3k Inhibitor ◽  
Phosphatidylinositol 3 Kinase ◽  
Excitatory Amino Acid Transporter ◽  
Drug Concentrations ◽  
Pkc Inhibitors ◽  
Acid Transporter ◽  
Type 3

We investigated the effects of flumazenil, aminophylline, and ephedrine on the excitatory amino acid transporter type 3 (EAAT3) activity and the interaction with propofol. EAAT3 was expressed in the Xenopus oocytes. L-Glutamate-induced membrane currents were measured using the two-electrode voltage clamp at various drug concentrations. Oocytes were preincubated with protein kinase C- (PKC-) activator, or inhibitor, and phosphatidylinositol 3-kinase (PI3K) inhibitor. To study the interaction with propofol, oocytes were exposed to propofol, propofol + aminophylline, or ephedrine. Aminophylline and ephedrine significantly decreased EAAT3 activity. Aminophylline (95 μM) and ephedrine (1.19 μM) significantly decreased Vmax, but not Km of EAAT3, for glutamate. The phorbol 12-myristate-13-acetate-induced increase in EAAT3 activity was abolished by aminophylline or ephedrine. The decreased EAAT3 activities by PKC inhibitors (staurosporine, chelerythrine) and PI3K inhibitor (wortmannin) were not significantly different from those by aminophylline or ephedrine, as well as those by PKC inhibitors or PI3K inhibitor + aminophylline or ephedrine. The enhanced EAAT3 activities induced by propofol were significantly abolished by aminophylline or ephedrine. Aminophylline and ephedrine inhibit EAAT3 activity via PKC and PI3K pathways and abolish the increased EAAT3 activity by propofol. Our results indicate a novel site of action for aminophylline and ephedrine.

Ondansetron attenuates the activity of excitatory amino acid transporter type 3 expressed in Xenopus oocytes

2014 ◽  
Vol 733 ◽  
pp. 7-12 ◽  
Author(s):  
Wonseok Hur ◽  
Mi Kyoung Lee ◽  
Hee-Pyeong Park ◽  
Chong-Sung Kim ◽  
Hea-Jo Yoon ◽  
...  
Keyword(s):  
Amino Acid ◽  
Xenopus Oocytes ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporter ◽  
Excitatory Amino Acid Transporter ◽  
Acid Transporter ◽  
Type 3
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