title: Characteristic expressions of GABA receptors and GABA producing/transporting molecules in rat kidney.
abstract: Gamma-aminobutyric acid (GABA) is an important neurotransmitter, but recent reports have revealed the expression of GABAergic components in peripheral, non-neural tissues. GABA administration induces natriuresis and lowers blood pressure, suggesting renal GABA targets. However, systematic evaluation of renal GABAergic components has not been reported. In this study, kidney cortices of Wistar-Kyoto rats (WKY) were used to assay for messenger RNAs of GABA-related molecules using RT-PCR. In WKY kidney cortex, GABAA receptor subunits, α1, β3, δ, ε and π, in addition to both types of GABAB receptors, R1 and R2, and GABAC receptor ρ1 and ρ2 subunit mRNAs were detected. Kidney cortex also expressed mRNAs of glutamate decarboxylase (GAD) 65, GAD67, 4-aminobutyrate aminotransferase and GABA transporter, GAT2. Western blot and/or immunohistochemistry were performed for those molecules detected by RT-PCR. By immunofluorescent observation, co-staining of α1, β3, and π subunits was observed mainly on the apical side of cortical tubules, and immunoblot of kidney protein precipitated with π subunit antibody revealed α1 and β3 subunit co-assembly. This is the first report of GABAA receptor π subunit in the kidney. In summary, unique set of GABA receptor subunits and subtypes were found in rat kidney cortex. As GABA producing enzymes, transporters and degrading enzyme were also detected, a possible existence of local renal GABAergic system with an autocrine/paracrine mechanism is suggested.
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Midori Sasaki
authors.initials: MS
authors.lastname: Yatabe
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sanada
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima, Japan; Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yatabe
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C493418:SLC6A13 protein, human; C092004:Slc6a13 protein, rat; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2