title: Progesterone increases the activity of glutamate transporter type 3 expressed in Xenopus oocytes.
abstract: Progesterone is an important sex hormone for pregnancy and also has neuroprotective and anticonvulsant effects. It is well-known that full-term parturients become more susceptible to volatile anesthetics. Glutamate transporters are important for preventing neurotoxicity and anesthetic action in the central nervous system. We investigated the effects of progesterone on the activity of glutamate transporter type 3 (EAAT3), the major neuronal EAAT. EAAT3 was expressed in Xenopus laevis oocytes by injecting its mRNA. Oocytes were incubated with diluted progesterone for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 μML-glutamate. Progesterone (1-100 nM) significantly increased EAAT3 activity in a dose-dependent manner. Our kinetic study showed that the Vmax was increased in the progesterone group compared with that in the control group (2.7 ± 0.2 vs. 3.6 ± 0.2μC for control group vs. progesterone group; n=18-23; P<0.05), however, Km was unaltered (46.7 ± 10.2μM vs. 55.9 ± 10.5μM for control group vs. progesterone group; n=18-23; P>0.05). Phorbol-12-myristate-13-acetate, a protein kinase C (PKC) activator, did not change progesterone-enhanced EAAT3 activity. Inhibitors of PKC or phosphatidylinositol 3-kinase (PI3K) abolished the progesterone-induced increases in EAAT3 activity. Our results suggest that progesterone enhances EAAT3 activity and that PKC and PI3K are involved in mediating these effects. These effects of progesterone may contribute to its anticonvulsant and anesthesia-related properties.
authors.affiliation: Department of Anesthesiology & Pain Medicine, Konkuk University School of Medicine, Seoul, South Korea.
authors.forename: Ilsoon
authors.initials: I
authors.lastname: Son
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Ryu
authors.forename: Hae-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Sang-Hwan
authors.initials: SH
authors.lastname: Do
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D009865:Oocytes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D014981:Xenopus / Q000235:genetics*
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493398:Slc1a1 protein, rat; D011374:Progesterone; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C
keywords: Excitatory amino acid transporter type 3; Glutamate transporter; Phosphatidylinositol 3-kinase; Progesterone; Protein kinase C; Xenopus oocyte