Agmatine Uptake by Cultured Hamster Kidney Cells

doi:10.1006/bbrc.2000.4101

Biochemical and Biophysical Research Communications

Volume 280, Issue 1, 12 January 2001, Pages 307-311

https://doi.org/10.1006/bbrc.2000.4101 Get rights and content

Abstract

Agmatine, the product of arginine decarboxylation, has been recently found in a wide variety of animal tissues. In spite of the emergent interest on agmatine in animals, the mechanism of agmatine uptake in mammalian cells has been scarcely studied. An analysis of radiolabeled agmatine uptake was carried out by using a classical, kinetic approach with BHK-21 hamster kidney cells in culture. A high affinity, temperature- and energy-dependent agmatine transport system in BHK-21 kidney cells is here kinetically characterized which seems to be a “general” transporter shared by di- and triamines and different to a highly specific carrier for the tetraamine spermine.

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Citation Excerpt :
Finally, an identity of the uptake system with the P-glycoprotein transport process was ruled out. The pharmacological characteristics of the agmatine uptake determined in the intestinal cell lines and the human glioma cell line SK-MG-1 resembled those (Table 1) of the selective agmatine uptake detected in rat arterial endothelial cells (Babal et al., 2000), hamster kidney cells (del Valle et al., 2001), fibroblast-derived Ras/3T3 cells (Satriano et al., 2001a) and rat spinal synaptosomes (Goracke-Postle et al., 2006). In contrast to our findings, Gründemann et al., reported an efficient transport of [3H]agmatine by OCT2 and OCT3 but not OCT1 in HEK 293 cells stably transfected with hOCT1, hOCT2 and hOCT3 (Gründemann et al., 2003; Table 1).
Agmatine, a cationic amine formed by decarboxylation of l-arginine by the mitochondrial enzyme arginine decarboxylase (ADC), is widely but unevenly distributed in mammalian tissues. Agmatine in the tissues originates from cellular enzymatic de novo synthesis and from agmatine absorbed from the lumen of the gut. Absorption from the gut and accumulation in the tissues and cells must occur via a specific carrier mechanism because the compound is charged at physiologic pH and, hence, biological membranes are almost completely impermeable to the organic cation in the absence of an uptake system. Agmatine initially attracted attention as an endogenous ligand at imidazoline receptors and α₂-adrenoceptors. However, independent of binding to those receptors, agmatine induces a variety of physiological and pharmacological effects exhibiting a great therapeutic potential of the compound. Although the precise function of endogenous agmatine is presently still unclear, this review summarizes the current knowledge concerning the physiological and pathophysiological function of agmatine.
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Amines such as agmatine, putrescine, spermidine and spermine have been reported to be involved in a variety of physiological and biochemical phenomena. However, it is not known whether they are also involved in the homeostasis of intracellular fibronectin content via upregulation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and transforming growth factor-β1 (TGF-β1). To determine this, we have studied the effect of multiple amines on fibronectin, TGF-β1, ERK, and PKC levels in mesangial cells under high glucose conditions. All the amines tested (at 0.1–1 mM) affected neither the viability of mesangial cells for 42 h nor LDH release into the medium. Agmatine reduced TGF-β1 and ERK levels but not PKC at concentrations of 0.1–1 mM. However, levels of fibronectin, TGF-β1, ERK, and PKC were unaffected by either putrescine or spermidine. A decrease in fibronectin secretion was accompanied by decreases in TGF-β1 and ERK. Such cumulative results lead us to hypothesize that agmatine reduces high glucose-induced fibronectin secretion via several pathways including ERK–TGF-β1–fibronectin and spermine, via a decrease in TGF-β1. Possible roles of enzymes involved in agmatine and polyamine biosynthesis are discussed in relation to secretion of ECM proteins.
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Regular ArticleAgmatine Uptake by Cultured Hamster Kidney Cells

Abstract

Cell

J. Biol. Chem.

Anal. Biochem.

Life Sci.

Biochem. Pharmacol.

J. Biol. Chem.

Kidney Int.

Anal. Biochem.

Int. J. Biochem. Cell. Biol.

Int. J. Biochem.

J. Biol. Chem.

J. Biol. Chem.

Arginine metabolism: Nitric oxide and beyond

Biochem. J.

Agmatine: An endogenous clonidine-displacing substance in the brain

Science

Imidazoline recognition sites and stomach function

Ann. N.Y. Acad. Sci.

Partial cloning and characterization of an arginine decarboxylase in the kidney

Kidney Int.

Agmatine is synthesized by a mitochondrial arginine decarboxylase in rat brain

Ann. N.Y. Acad. Sci.

Regular Article
Agmatine Uptake by Cultured Hamster Kidney Cells