TY - JOUR
T1 - Reserpine binding to a vesicular amine transporter expressed in Chinese hamster ovary fibroblasts
AU - Schuldiner, Shimon
AU - Liu, Yongjian
AU - Edwards, Robert H.
PY - 1993/1/5
Y1 - 1993/1/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0027476079&partnerID=8YFLogxK
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C2 - 8416935
AN - SCOPUS:0027476079
SN - 0021-9258
VL - 268
SP - 29
EP - 34
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -