Abstract：
:In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyridine derivative (-)-[(3)H]BZDC-DHP, a recently developed high-affinity ligand for Mdr1, binds with similar affinity to ZG membranes (ZGM) (K(d) = 6.2 nM). Binding was inhibited by nanomolar concentrations of the L-type Ca(2+) channel blockers azidopine and verapamil and by micromolar concentrations of the K(+) channel blockers glibenclamide and quinidine. Inhibition by glibenclamide was noncompetitive. The Mdr1 modulators cyclosporin A and vinblastine did not inhibit binding, which is different from Mdr1. In addition, only (+/-)-BZDC-DHP, azidopine, and verapamil selectively inhibited the K(+) conductance in ZGs, whereas the Cl(-) conductance was not affected. In photoaffinity labeling experiments, (-)-[(3)H]BZDC-DHP surprisingly specifically and selectively labeled a approximately 19-kDa protein in ZGM with a pharmacological profile identical with the high-affinity binding site but did not label a 65-kDa protein. The 19-kDa protein was purified by ion exchange chromatography and SDS-polyacrylamide gel electrophoresis and sequenced. The sequence obtained corresponds to ZG-16p, a recently cloned ZG protein with no apparent homology to Mdr1. The identity of the 19-kDa protein was confirmed by immunoprecipitation of (-)-[(3)H]BZDC-DHP-labeled ZGM with an anti-ZG-16p antibody. Furthermore, it is shown that ZG-16p is associated with the ZGM. We propose that ZG-16p, as part of the submembranous granule matrix, regulates the ATP-sensitive K(+) conductance of ZGs.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Braun M,Thévenod Fkeywords:
subject
Has Abstractpub_date
2000-02-01 00:00:00pages
308-16issue
2eissn
0026-895Xissn
1521-0111journal_volume
57pub_type
杂志文章abstract：:Retinoid X receptor α [RXRα; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRα undergoes rapid post-translational modifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, wh...
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pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
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更新日期：2003-06-01 00:00:00
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更新日期：1985-05-01 00:00:00
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doi：
更新日期：1996-05-01 00:00:00
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更新日期：2001-03-01 00:00:00
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更新日期：1994-10-01 00:00:00
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更新日期：1999-04-01 00:00:00
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更新日期：1995-10-01 00:00:00
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更新日期：1987-02-01 00:00:00
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更新日期：1992-05-01 00:00:00
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更新日期：1994-04-01 00:00:00
