Reserpine binding to a vesicular amine transporter expressed in Chinese hamster ovary fibroblasts

Shimon Schuldiner*, Yongjian Liu, Robert H. Edwards

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The potent antihypertensive drug reserpine inhibits the transport of biogenic amines into adrenal chromaffin granules and synaptic vesicles. Reserpine acts by binding almost irreversibly to the vesicular amine transporter, and this interaction has been used both to study the mechanism of transport and to purify the protein responsible. Recent isolation of a cDNA for the rat chromaffin granule amine transporter (CGAT) by selection in the neurotoxin 1-methyl-4-phenylpyridin-ium now permits an analysis of the interaction with reserpine at a molecular level. Using membranes from stable transformants expressing the transporter, we show that reserpine binds specifically and quantitatively to CGAT. As with the native protein in bovine chromaffin granules, a pH gradient accelerates reserpine binding, and amine substrates compete for binding with reserpine. However, 1-methyl-4-phenylpyridinium and tetrabenazine, the other principal inhibitor of vesicular amine transport, compete very poorly with reserpine for binding, suggesting that they interact with CGAT at distinct sites.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number1
StatePublished - 5 Jan 1993

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