Polyamine transport system mediates agmatine transport in mammalian cells |
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Authors: | Satriano J Isome M Casero R A Thomson S C Blantz R C |
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Affiliation: | Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs Medical Center, La Jolla, California 92161, USA. jsatriano@ucsd.edu |
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Abstract: | Agmatine is a biogenic amine with the capacity toregulate a number of nonreceptor-mediated functions in mammalian cells, including intracellular polyamine content and nitric oxide generation. We observed avid incorporation of agmatine into several mammalian celllines and herein characterize agmatine transport in mammalian cells. Intransformed NIH/3T3 cells, agmatine uptake is energy dependent with asaturable component indicative of carrier-mediated transport. Transportdisplays an apparent Michaelis-Menten constant of 2.5 µM and amaximal velocity of 280 pmol · min1 · mg1 proteinand requires a membrane potential across the plasma membrane foruptake. Competition with polyamines, but not cationic molecules thatutilize the y+ system transporter, suppresses agmatineuptake. Altering polyamine transporter activity results in parallelchanges in polyamine and agmatine uptake. Furthermore, agmatine uptakeis abrogated in a polyamine transport-deficient human carcinoma cellline. These lines of evidence demonstrate that agmatine utilizes, and is dependent on, the polyamine transporter for cellular uptake. Thefact that this transport system is associated with proliferation couldbe of consequence to the antiproliferative effects of agmatine. |
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