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Pharmacology

Progesterone increases the activity of glutamate transporter type 3 expressed in Xenopus oocytes: 9AP5-3

Sang-Hwan, D.; Hye-Min, S.; Seong-Joo, P.; Jung-Hee, R.; Mi-Hyeon, K.; Il-Soon, S.

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European Journal of Anaesthesiology: June 2012 - Volume 29 - Issue - p 143
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Background and Goal of Study: Progesterone is an important sex hormone for pregnancy and also has neuroprotective and antiepileptic effects as a neurosteroid hormone. It is well known that minimum alveolar concentration (MAC) of inhalation anesthetics is reduced during pregnancy. Glutamate transporters are important for preventing neurotoxicity and for anesthetic action in the central nervous system. The authors investigated the effects of progesterone on the activity of glutamate transporter type 3 (EAAT3).

Materials and Methods: EAAT3 was expressed in Xenopus oocytes by injecting its mRNA. Oocytes were incubated with diluted progesterone for 72 hours. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying L-glutamate (30 μM). Responses were quantified by integrating the current traces and reported in microCoulombs (μC). Results are presented as mean±S.E.M.

Results and Discussion: Progesterone concentration from 1 to 100 nM significantly increased the responses in a dose-dependent manner. Kinetic study showed that Vmax was increased compared with control group (2.7±0.2 μC for control group vs. 3.6±0.2 μC for progesterone group; n=13-16; p< 0.05), but Km was not changed (46.7±10.2 nM for control group vs. 55.9±10.5 nM for progesterone group; n=13-16; p>0.05). Phorbol-12-myristate-13-acetate, a protein kinase C (PKC) activator did not change progesterone-induced EAAT3 activity. Staurosporine, a protein kinase C inhibitor and wortmannin, phosphatidylinositol 3-kinase (PI3K) inhibitor abolished the progesteroneinduced increases of EAAT3 activity.

Conclusion(s): Our results suggest that progesterone increases the EAAT3 activity and that PKC and PI3K may mediate this effect. This effects of progesterone may explain its neuroprotective and anesthesia-related properties.

References:

Danbolt NC. Glutamate uptake. Prog Neurobiol 2001; 65: 1-105. Do SH, Ham BM, Zuo Z. Effects of propofol on the activity of rat glutamate transporter type 3 expressed in Xenopus oocytes: the role of protein kinase C. Neurosci Lett 2003; 343: 113-6.
    © 2012 European Society of Anaesthesiology