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Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain

Huber, Robert D. and Gao, Bo and Sidler Pfändler, Marguerite-Anne and Zhang-Fu, Wenting and Leuthold, Simone and Hagenbuch, Bruno and Folkers, Gerd and Meier, Peter J. and Stieger, Bruno. (2007) Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain. American journal of physiology. Cell physiology, Vol. 292, H. 2 , C795-C806.

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Official URL: http://edoc.unibas.ch/dok/A5261580

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Abstract

In the present study we isolated two splice variants of organic anion transporting polypeptide 3A1 (OATP3A1_v1 and OATP3A1_v2) from human brain. OATP3A1_v2 lacks 18 amino acids (aa) at the COOH-terminal end (692 aa) but is otherwise similar in sequence to OATP3A1_v1 (710 aa). OATP3A1_v1 exhibits a wide tissue distribution, with expression in testis, various brain regions, heart, lung, spleen, peripheral blood leukocytes, and thyroid gland, whereas OATP3A1_v2 is predominantly expressed in testis and brain. On the cellular and subcellular levels OATP3A1_v1 could be immunolocalized in testicular germ cells, the basolateral plasma membrane of choroid plexus epithelial cells, and neuroglial cells of the gray matter of human frontal cortex. Immunolocalization of OATP3A1_v2 included Sertoli cells in testis, apical and/or subapical membranes in choroid plexus epithelial cells, and neurons (cell bodies and axons) of the gray and white matter of human frontal cortex. The rodent ortholog Oatp3a1 was also widely distributed in rat brain, and its localization included somatoneurons as well as astroglial cells. Transport studies in cRNA-injected Xenopus laevis oocytes and in stably transfected Chinese hamster ovary FlpIn cells revealed a similar broad substrate specificity for both splice variants. Transported substrates include prostaglandin (PG)E(1) and PGE(2), thyroxine, and the cyclic oligopeptides BQ-123 (endothelin receptor antagonist) and vasopressin. These studies provide further evidence for the involvement of OATPs in oligopeptide transport. They specifically suggest that OATP3A1 variants might be involved in the regulation of extracellular vasopressin concentration in human brain and thus might influence the neuromodulation of neurotransmission by cerebral neuropeptides such as vasopressin.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Physiological Society
ISSN:0002-9513
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:21
Deposited On:22 Mar 2012 13:23

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