| Title | Clonidine accumulation in human neuronal cells. | | Author(s) | Fischer W, Neubert RH, Brandsch M | | Institution | Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, D-06120 Halle, Germany. | | Source | Eur J Pharm Sci 2007 Aug 10. | | Abstract | After transport across several epithelial barriers including the blood-brain barrier, clonidine interacts with alpha(2)-adrenergic receptors and imidazoline binding sites in the brain. We hypothesized that neuronal cells take up clonidine thereby removing the drug from the extracellular fluid compartment. Uptake of [(3)H]clonidine into SH-SY5Y neuroblastoma cells was linear for up to 1min, unaffected by inside directed Na(+) or Cl(-) gradients but strongly inhibited by an outside pH of 6.0. The cells accumulated [(3)H]clonidine 50-70-fold uphill against a concentration gradient. Unlabeled clonidine, guanabenz, imipramine, diphenhydramine, maprotiline, quinine and the endogenous monoamine phenylethylamine (2mM) strongly inhibited the [(3)H]clonidine uptake by 60-95%. Tetraethylammonium, choline and N-methyl-4-phenylpyridinium had no effect. The accumulation at pH 7.5 was saturable with an apparent Michaelis-Menten constant (K(t)) of 0.7mM. We conclude that SH-SY5Y cells not only bind clonidine to extracellular receptors but also take up the drug rapidly by a specific and concentrative mechanism. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17869491 |
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