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[Elucidation of New Function in Endothelial Cells for Efficient Delivery Strategy of Drug to Tissues].
- Source :
-
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan [Yakugaku Zasshi] 2020; Vol. 140 (1), pp. 51-62. - Publication Year :
- 2020
-
Abstract
- The author has described two new functions of endothelial cells for efficient delivery of drugs to tissues. First, it was indicated that tight junction (TJ)-associated protein, claudin-1, exerts potent paracellular barrier function in cultured mouse lung microvascular endothelial cells (LMECs). This barrier was instantly and reversibly opened by reduction of TJ proteins expression via histamine H <subscript>1</subscript> and H <subscript>2</subscript> receptors. Histamine was biosynthesized by l-histidine decarboxylase from uptaken l-histidine, and biotransformed by type B of monoamine oxidase, suggesting that histamine concentration is controlled in rat brain MECs (BMECs) and LMECs. Moreover, uptake of l-histidine into BMECs and LMECs markedly increased with addition of ZnSO <subscript>4</subscript> . Second, it was suggested that drug-metabolizing enzymes such as CYP and flavin-containing monooxygenase exist in vascular endothelial cells exposed to blood and to aerobic conditions. These cells have the same ability to metabolize drugs as hepatocytes, demonstrating that vascular endothelial cells are a metabolic barrier against tissue transfer of drugs. From these results, it was suggested that reversible opening of TJ and selective inhibition of drug metabolism in vascular endothelial cells may be efficient delivery strategies of drugs to tissues. Finally, I hope that this research will lead to development of new drugs and possible re-evaluation of discontinued drugs.
- Subjects :
- Animals
Cells, Cultured
Claudin-1 genetics
Claudin-1 metabolism
Cytochrome P-450 Enzyme System metabolism
Endothelial Cells metabolism
Gene Expression
Histamine biosynthesis
Histidine metabolism
Mice
Mixed Function Oxygenases metabolism
Rats
Receptors, Histamine H1
Receptors, Histamine H2
Drug Delivery Systems
Endothelial Cells enzymology
Endothelial Cells physiology
Subjects
Details
- Language :
- Japanese
- ISSN :
- 1347-5231
- Volume :
- 140
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
- Publication Type :
- Academic Journal
- Accession number :
- 31902886
- Full Text :
- https://doi.org/10.1248/yakushi.19-00179