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Background    para -Tyramine ( p -TA) is a biogenic amine which is involved in multiple neuronal signal transductions. Since the concentration of  p -TA in dog cerebrospinal fluid (CSF) has been reported to be greater than that in plasma, it is proposed that clearance of cerebral  p -TA is important for normal function. The purpose of this study was to examine the role of the blood–brain barrier and blood-cerebrospinal fluid barrier (BCSFB) in  p -TA clearance from the brain.    Methods  In vivo [ 3 H] p -TA elimination from rat cerebral cortex and from CSF was examined after intracerebral and intracerebroventricular administration, respectively. To evaluate BCSFB-mediated  p -TA transport, [ 3 H] p -TA uptake by isolated rat choroid plexus and conditionally immortalized rat choroid plexus epithelial cells, TR-CSFB3 cells, was performed.    Results  The half-life of [ 3 H] p -TA elimination from rat CSF was found to be 2.9 min, which is 62-fold faster than that from rat cerebral cortex. In addition, this [ 3 H] p -TA elimination from the CSF was significantly inhibited by co-injection of excess unlabeled  p -TA. Thus, carrier-mediated  p -TA transport process(es) are assumed to take part in  p -TA elimination from the CSF. Since it is known that transporters at the BCSFB participate in compound elimination from the CSF, [ 3 H] p -TA transport in ex vivo and in vitro models of rat BCSFB was examined. The [ 3 H] p -TA uptake by isolated rat choroid plexus and TR-CSFB3 cells was time-dependent and was inhibited by unlabeled  p -TA, indicating carrier-mediated  p -TA transport at the BCSFB. The  p -TA uptake by isolated choroid plexus and TR-CSFB3 cells was not reduced in the absence of extracellular Na +  and Cl − , and in the presence of substrates of typical organic cation transporters. However, this  p -TA uptake was significantly inhibited by cationic drugs such as propranolol, imipramine, amantadine, verapamil, and pyrilamine. Moreover,  p -TA uptake by TR-CSFB3 cells took place in an oppositely-directed H +  gradient manner. Therefore, this suggested that  p -TA transport at the BCSFB involves cationic drug-sensitive transport systems which are distinct from typical plasma membrane organic cation transporters.    Conclusion  Our study indicates that  p -TA elimination from the CSF is greater than that from the cerebral cortex. Moreover, it is suggested that cationic drug-sensitive transport systems in the BCSFB participate in this  p -TA elimination from the CSF.

Role of cationic drug-sensitive transport systems at the blood-cerebrospinal fluid barrier in para-tyramine elimination from rat brain