title: Calmodulin-associated post-translational regulation of rat organic cation transporter 2 in the kidney is gender dependent.
abstract: In this work, regulation of organic cation transporter type 2 from rat (rOCT2) stably transfected in HEK293 cells was investigated by microfluorimetry with 4-(4-(dimethylamino)styryl)-N-methylpyridinium as substrate. The transport mediated by rOCT2 was specifically stimulated by PKA, phosphatidylinositol-3-kinase, p56(lck) tyrosine kinase, mitogen-extracellular-signal-regulated-kinase-1/2, calmodulin (CaM), and CaM-kinase-II. The regulatory pattern of rOCT2 differs markedly quantitatively and qualitatively from that of other OCT isoforms. Only CaM-dependent upregulation is conserved throughout the OCT family. For this reason, CaM regulation of rOCT2 was also investigated in isolated S3-segments (known to express only rOCT2) of male and female rat proximal tubules. Inhibition of CaM by calmidazolium significantly decreased rOCT2 activity (-49.0 +/- 13.6%, n = 4) in male but not female (9.0 +/- 13.0%, n = 4) rats. Real-time PCR and Western blot investigations of CaM expression in rat kidneys showed that male animals have significantly higher CaM expression. This is the first study describing post-translational gender-dependent rOCT2 regulation.
authors.affiliation: Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Domagkstrasse 3a, 48149, Münster, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wilde
authors.forename: E
authors.initials: E
authors.lastname: Schlatter
authors.forename: H
authors.initials: H
authors.lastname: Koepsell
authors.forename: B
authors.initials: B
authors.lastname: Edemir
authors.forename: S
authors.initials: S
authors.lastname: Reuter
authors.forename: H
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: U
authors.initials: U
authors.lastname: Neugebauer
authors.forename: R
authors.initials: R
authors.lastname: Schröter
authors.forename: S
authors.initials: S
authors.lastname: Brast
authors.forename: G
authors.initials: G
authors.lastname: Ciarimboli