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-His²) thyrotropin-releasing hormone ([³H]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 [³H]MeTRH after intravenous (i.v.) injection in mice. Furthermore, the capillary depletion method was performed to determine whether [³H]MeTRH crossed the blood-brain barrier. The effects of TRH and its analogues on the brain distribution of [³H]MeTRH were also examined by co-injection with the radioligand. The brain distribution of [³H]MeTRH and [¹⁴C]sucrose increased with the time after i.v. injection in mice, and the level of [³H]MeTRH was significantly higher than that of [¹⁴C]sucrose 5 min after the injection. The CL_in value of [³H]MeTRH was significantly higher than that of [¹⁴C]sucrose, and the value of [³H]MeTRH was reduced by co-injection with unlabeled MeTRH. Also, capillary depletion showed that [³H]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 [³H]MeTRH into the brain may be via a saturable process.