The orally active antihyperglycemic drug β-guanidinopropionic acid is transported by the human proton-coupled amino acid transporter hPAT1

Molecular Pharmaceutics

Volumn 6, Issue 3, 2009, Pages 1006-1011

  Metzner, Linda ^a   Dorn, Madlen ^a   Markwardt, Fritz ^a   Brandsch, Matthias ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

guanidinopropionic acid ( GPA); Antihyperglycemic; Caco 2 cells; Drug delivery; Human h + coupled amino acid transporter hPAT1; Intestinal barrier; Voltage clamp; Xenopus laevis oocytes

Indexed keywords

4 GUANIDINOBUTYRIC ACID; AMINO ACID TRANSPORTER; GUANIDINOACETIC ACID; GUANIDINOPROPIONIC ACID; ORAL ANTIDIABETIC AGENT; PROTON;

APICAL MEMBRANE; ARTICLE; CELL STRAIN CACO 2; CONTROLLED STUDY; DRUG PROTEIN BINDING; DRUG TRANSPORT; ELECTROPHYSIOLOGY; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; INTESTINE CELL; NONHUMAN; OOCYTE; PRIORITY JOURNAL; XENOPUS LAEVIS;

AMINO ACID TRANSPORT SYSTEMS; ANTILIPEMIC AGENTS; BIOLOGICAL TRANSPORT; CACO-2 CELLS; ELECTROPHYSIOLOGY; GLYCINE; GUANIDINES; HUMANS; KINETICS; MOLECULAR STRUCTURE; PROLINE; SYMPORTERS;

EID: 67249150155     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp9000684     Document Type: Article

References (25)

1. Meglasson, M. D.; Wilson, J. M.; Yu, J. H.; Robinson, D. D.; Wyse, B. M.; de Souza, C. J. Antihyperglycemic action of guanidinoalkanoic acids: 3-guanidinopropionic acid ameliorates hyperglycemia in diabetic KKAy and C57BL6Job/ob mice and increases glucose disappearance in rhesus monkeys. J. Pharmacol. Exp. Ther. 1993, 266, 1454-1462. (Pubitemid 24175791)
2. Vaillancourt, V. A.; Larsen, S. D.; Tanis, S. P.; Burr, J. E.; Connell, M. A.; Cudahy, M. M.; Evans, B. R.; Fisher, P. V.; May, P. D.; Meglasson, M. D.; Robinson, D. D.; Stevens, F. C.; Tucker, J. A.; Vidmar, T. J.; Yu, J. H. Synthesis and biological activity of aminoguanidine and diaminoguanidine analogues of the antidiabetic/antiobesity agent 3-guanidinopropionic acid. J. Med. Chem. 2001, 44, 1231-1248. (Pubitemid 32861758)
3. De Tata, V.; Cavallini, G.; Pollera, M.; Gori, Z.; Bergamini, E. The induction of mitochondrial myopathy in the rat by feeding beta- guanidinopropionic acid and the reversibility of the induced mitochondrial lesions: a biochemical and ultrastructural investigation. Int. J. Exp. Pathol 1993, 74, 501-509. (Pubitemid 23304086)
4. Pandke, K. E.; Mullen, K. L.; Snook, L. A.; Bonen, A.; Dyck, D. J. Decreasing intramuscular phosphagen content simultaneously increases plasma membrane FAT/CD36 and GLUT4 transporter abundance. Am. J. Physiol. 2008, 295, R806-R813.
5. Ren, J. M.; Semenkovich, C. F.; Holloszy, J. O. Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. Am. J. Physiol. 1993, 264, C146-C150. (Pubitemid 23057494)
6. Yaspelkis, B. B., 3rd; Castle, A. L.; Farrar, R. P.; Ivy, J. L. Effect of chronic electrical stimulation and beta-GPA diet on GLUT4 protein concentration in rat skeletal muscle. Acta Physiol. Scand. 1998, 163, 251-259.
7. Frøsig, C.; Rose, A. J.; Treebak, J. T.; Kiens, B.; Richter, E. A.; Wojtaszewski, J. F. Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. Diabetes 2007, 56, 2093-2102. (Pubitemid 47195824)
8. Wiernsperger, N. F.; Bailey, C. J. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs 1999, 58, 31-39. (Pubitemid 129758579)
9. Boll, M.; Foltz, M.; Rubio-Aliaga, I.; Kottra, G.; Daniel, H. Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters. J. Biol. Chem. 2002, 277, 22966-22973. (Pubitemid 34967281)
10. Sagné, C.; Agulhon, C.; Ravassard, P.; Darmon, M.; Hamon, M.; El Mestikawy, S.; Gasnier, B.; Giros, B. Identification and characterization of a lysosomal transporter for small neutral amino acids. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 7206-7211. (Pubitemid 32567927)
11. Chen, Z.; Fei, Y. J.; Anderson, C. M.; Wake, K. A.; Miyauchi, S.; Huang, W.; Thwaites, D. T.; Ganapathy, V. Structure, function and immunolocalization of a proton-coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco-2. J. Physiol. 2003, 546, 349-361. (Pubitemid 36175972)
12. Anderson, C. M.; Grenade, D. S.; Boll, M.; Foltz, M.; Wake, K. A.; Kennedy, D. J.; Munck, L. K.; Miyauchi, S.; Taylor, P. M.; Campbell, F. C.; Munck, B. G.; Daniel, H.; Ganapathy, V.; Thwaites, D. T. H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat. Gastroenterology 2004, 127, 1410-1422. (Pubitemid 39457768)
13. Brandsch, M. Transport of L-proline, L-proline-containing peptides and related drugs at mammalian epithelial cell membranes. Amino Acids 2006, 31, 119-136. (Pubitemid 44222574)
14. +-coupled amino-acid transporter hPAT1. Br. J. Pharmacol. 2006, 147, 298-306.
15. Metzner, L.; Kalbitz, J.; Brandsch, M. Transport of pharmacologically active proline derivatives by the human proton-coupled amino acid transporter hPAT1. J. Pharmacol. Exp. Ther. 2004, 309, 28-35. (Pubitemid 38393110)
16. Metzner, L.; Natho, K.; Zebisch, K.; Dorn, M.; Bosse-Doenecke, E.; Ganapathy, V.; Brandsch, M. Mutational analysis of histidine residues in the human proton-coupled amino acid transporter PAT1. Biochim. Biophys. Acta 2008, 1778, 1042-1050.
17. Riedel, T.; Lozinsky, I.; Schmalzing, G.; Markwardt, F. Kinetics of P2X7 receptor-operated single channels currents. Biophys. J. 2007, 92, 2377-2391. (Pubitemid 46536420)
18. Klapperstück, M.; Büttner, C.; Böhm, T.; Schmalzing, G.; Markwardt, F. Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes. Biochim. Biophys. Acta 2000, 1467, 444-456. (Pubitemid 30665596)
19. Bretschneider, F.; Markwardt, F. Drug-dependent ion channel gating by application of concentration jumps using U-tube technique. Methods Enzymol. 1999, 294, 180-189. (Pubitemid 28483358)
20. Metzner, L.; Kottra, G.; Neubert, K.; Daniel, H.; Brandsch, M. Serotonin, L-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J. 2005, 19, 1468-1473. (Pubitemid 41279005)
21. Hiraga, Y.; Kinoshita, T. High-performance liquid chromatographic analysis of guanidino compounds using ninhydrin reagent. II. Guanidino compounds in blood of patients on haemodialysis therapy. J. Chromatogr. 1985, 342, 269-275.
22. Watanabe, C. K. Studies in the metabolism changes induced by administration of guanidine bases. I. Influence of injected guanidine hydrochloride upon blood sugar content. J. Biol. Chem. 1918, 33, 253-265.
23. Meglasson, M. D. (Inventor) Use of 3-guanidinopropionic acid in the treatment of non-insulin dependent diabetes mellitus (NIDDM). U.S. Patent 5,132,324 (Application number 07/712862), 1992.
24. Nash, S. R.; Giros, B.; Kingsmore, S. F.; Rochelle, J. M.; Suter, S. T.; Gregor, P.; Seldin, M. F.; Caron, M. G. Cloning, pharmacological characterization, and genomic localization of the human creatine transporter. Recept. Channels 1994, 2, 165-174. (Pubitemid 24262703)
25. - -creatine transporter: functional, molecular characterization and localization. J. Physiol. 2002, 545, 133-144.