Inhibition of agmatine transport in liver mitochondria by new charge-deficient agmatine analogues

被引：8
作者：
Grillo, M. A.
Battaglia, V.
Colombatto, S.
Rossi, C. A.
Simonian, A. R.
Salvi, M.
Khomutov, A. R.
Toninello, A. [1 ]
机构：
[1] Univ Padua, Inst Neurosci, CNR, Dept Biol Chem, Padua, Italy
[2] Univ Turin, Dept Med & Expt Oncol, Turin, Italy
[3] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia
来源：
BIOCHEMICAL SOCIETY TRANSACTIONS | 2007年 / 35卷
关键词：
agmatine; amino acid; guanidine compound; mitochondrion; polyamine; transport;
D O I：
10.1042/BST0350401
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The charge of the agmatine analogues AO-Agm [N-(3-aminooxypropyl)guanidine], GAPA [N-(3-amino-propoxy)guanidine] and NGPG [N-(3-guanidinopropoxy)guanidine] is deficient as compared with that of agmatine and they are thus able to inhibit agmatine transport in liver mitochondria. The presence of the guanidine group is essential for an optimal effect, since AO-Agm and NGPG display competitive inhibition, whereas that of GAPA is non-competitive. NGPG is the most effective inhibitor (K-i = 0.86 mM). The sequence in the inhibitory efficacy is not directly dependent on the degree of protonation of the molecules; in fact NGPG has almost the same charge as GAPA. When the importance of the guanidine group for agmatine uptake is taken into account, this observation suggests that the agmatine transporter is a single-binding, centre-gated pore rather than a channel.
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收藏
页码：401 / 404
页数：4
相关论文
共 23 条
[1]   Transport and metabolism of agmatine in rat hepatocyte cultures [J].
Cabella, C ;
Gardini, G ;
Corpillo, D ;
Testore, G ;
Bedino, S ;
Solinas, SP ;
Cravanzola, C ;
Vargiu, C ;
Grillo, MA ;
Colombatto, S .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (04) :940-947
[2]  
DELLAVIA L, 1999, ARCH BIOCHEM BIOPHYS, V365, P482
[3]   Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine [J].
Galea, E ;
Regunathan, S ;
Eliopoulos, V ;
Feinstein, DL ;
Reis, DJ .
BIOCHEMICAL JOURNAL, 1996, 316 :247-249
[4]   Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei [J].
Gorbatyuk, OS ;
Milner, TA ;
Wang, G ;
Regunathan, S ;
Reis, DJ .
EXPERIMENTAL NEUROLOGY, 2001, 171 (02) :235-245
[5]  
GORNALL AG, 1949, J BIOL CHEM, V177, P751
[6]   Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2) [J].
Gründemann, DG ;
Hahne, C ;
Berkels, R ;
Schömig, E .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (02) :810-817
[7]   Biosynthesis of agmatine in isolated mitochondria and perfused rat liver:: studies with 15N-labelled arginine [J].
Horyn, O ;
Luhovyy, B ;
Lazarow, A ;
Daikhin, Y ;
Nissim, A ;
Yudkoff, M ;
Nissim, I .
BIOCHEMICAL JOURNAL, 2005, 388 :419-425
[8]   Exposure of rat isolated stomach and rats in vivo to [14C]agmatine:: accumulation in the stomach wall and distribution in various tissues [J].
Molderings, GJ ;
Heinen, A ;
Menzel, S ;
Göthert, M .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2002, 16 (03) :219-225
[9]   Mammalian mitochondrial inner membrane cationic and neutral amino acid carriers [J].
Porter, RK .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2000, 1459 (2-3) :356-362
[10]   AGMATINE, THE BACTERIAL AMINE, IS WIDELY DISTRIBUTED IN MAMMALIAN-TISSUES [J].
RAASCH, W ;
REGUNATHAN, S ;
LI, G ;
REIS, DJ .
LIFE SCIENCES, 1995, 56 (26) :2319-2330
123