FUNCTIONAL CHARACTERIZATION OF RAT PLASMA MEMBRANE MONOAMINE TRANSPORTER (PMAT) IN THE BLOOD-BRAIN AND BLOOD-CEREBROSPINAL FLUID BARRIERS

• Published in: Archives of pharmacy practice 2012-01, Vol.3 (1), p.98-98
• Main Authors: Okura, Takashi, Kato, Sayaka, Morimoto, Riyo, Yui, Satoru, Yamashita, Atsushi, Terasaki, Tetsuya, Deguchi, Yoshiharu
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Dopamine; Membranes; Pharmaceutical sciences; Plasma; Rodents
• ISSN: 2320-5210; 2045-080X; 2045-080X

This study investigated the expression and functional roles of rat plasma membrane monoamine transporter (rPMAT) in the blood-brain barrier (BBB) and bloodcerebrospinal fluid barrier (BCSFB) by using in vitro brain barrier model cells (TRBBB13 and TR-CSFB3 cells) and multiple in vivo experimental techniques.1) Quantitative RT-PCR analysis showed relatively high expression of rPMAT mRNA in TR-BBB13 and TR-CSFB3 cells. 1-Methyl-4-phenylpyridinium (MPP+) was transported into rPMAT-expressing cells in a sodium-independent manner. [3H]MPP+ was taken up concentration-dependently by TR-BBB13 and TR-CSFB3 cells with Km values similar to that of rPMAT-expressing cells. [3H]MPP+ transports into these cells were markedly inhibited by serotonin, dopamine and cationic drugs. rPMAT siRNA significantly suppressed [3H]MPP+ uptake by TR-BBB13 cells. Intracerebrally injected [3H]MPP+ was eliminated from the brain parenchymal region, whereas brain [3H]MPP+ uptake did not increase with time during in situ brain perfusion, suggesting that the brain-to-blood transport across the BBB predominates over blood-to-brain transport. Brain microdialysis studies revealed that the elimination across the BBB was significantly decreased by co-perfusion of unlabelled MPP+, serotonin or dopamine. [3H]MPP+ was also eliminated from the CSF. These findings suggest that PMAT in brain barriers functions as the brain-to-blood transporter to regulate brain concentrations of organic cations, including monoamines and cationic neurotoxins.