title: Blood-brain permeability of [3H]-(3-methyl-His2)thyrotropin-releasing hormone (MeTRH) in mice: effects of TRH and its analogues.
abstract: The present study was undertaken to characterize the transport of (3-methyl-His(2)) thyrotropin-releasing hormone ([(3)H]MeTRH) across the blood-brain barrier in mice and the effects of thyrotropin-releasing hormone (TRH) and its analogues (taltirelin and montirelin) on the transport and brain distribution. Integration plot analysis was used to calculate the influx clearance (CL(in)) of [(3)H]MeTRH after intravenous (i.v.) injection in mice. Furthermore, the capillary depletion method was performed to determine whether [(3)H]MeTRH crossed the blood-brain barrier. The effects of TRH and its analogues on the brain distribution of [(3)H]MeTRH were also examined by co-injection with the radioligand. The brain distribution of [(3)H]MeTRH and [(14)C]sucrose increased with the time after i.v. injection in mice, and the level of [(3)H]MeTRH was significantly higher than that of [(14)C]sucrose 5 min after the injection. The CL(in) value of [(3)H]MeTRH was significantly higher than that of [(14)C]sucrose, and the value of [(3)H]MeTRH was reduced by co-injection with unlabeled MeTRH. Also, capillary depletion showed that [(3)H]MeTRH was distributed largely in the brain parenchyma and this distribution was significantly inhibited by co-injection of TRH and montirelin but not taltirelin. The present study indicates that the transport of [(3)H]MeTRH into the brain may be via a saturable process.
authors.affiliation: School of Pharmaceutical Sciences and COE21, University of Shizuoka, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Urayama
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohmori
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Deguchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kimura