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Nonlinear Intestinal Absorption of Fluorescein Isothiocyanate Dextran 4, 000 Caused by Absorptive and Secretory Transporting System

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DOI: 10.4236/pp.2011.23025    5,388 Downloads   10,191 Views   Citations

ABSTRACT

The mechanism of the nonlinear concentration dependence of the intestinal absorption of fluorescein isothiocyanate dextran 4,000 (FD-4) was studied using in situ rat intestinal loops and the in vitro Ussing-type chamber method. The intestinal absorption rate constant of FD-4, as evaluated by the intestinal loop method, increased significantly in a nonlinear fashion as the FD-4 concentration increased up to 0.2 mM and tended to decrease at concentrations higher than 0.2 mM. The mucosal-to-serosal permeation of FD-4 across rat ileal sheets, as evaluated by the in vitro Ussing-type chamber method, also increased in a nonlinear fashion in the low concentration range (0.01 - 0.02 mM), before decreasing as the concentration increased further, whereas serosal-to-mucosal permeation decreased in a concentration-dependent manner. In addition, mucosal-to-serosal flux and serosal-to-mucosal flux were increased and reduced in the presence of the metabolic inhibitor 2, 4-dinitrophenol, respectively. These results suggest that FD-4 is predominantly secreted into the intestinal lumen by an efflux transport system.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Tomita, R. Ohkubo, S. Ouchi, C. Kawahata and M. Hayashi, "Nonlinear Intestinal Absorption of Fluorescein Isothiocyanate Dextran 4, 000 Caused by Absorptive and Secretory Transporting System," Pharmacology & Pharmacy, Vol. 2 No. 3, 2011, pp. 173-179. doi: 10.4236/pp.2011.23025.

References

[1] J. S. Aranow, M. P. Fink. Determinant of intestinal bar- rier failure in critical illness. Br. J. Anesth., 77: 71-81 (1996).
[2] D. W. Riddington, B. Venkatesh, C. M. Boivin, R. S. Bonser, T. S. J. Elliott, T. Marshall, P. J. Mountford and J. F. Bion. Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonaly bypass. JAMA, 275: 1007-1012 (1996).
[3] P. L. Faries, R. J. Simon, A. T. Martella, M. J. Lee and G. W. Machiedo. Intestinal permeability correlates with se- verity of injury in trauma patients. J.Trauma, 44: 1031- 1036 (1998).
[4] H. M. Oudemans-van Straaten, P. G. Jansen, F. J. Hoek, S. J. van Deventer, A. Sturk, C. P. Stoutenbeek, G. N. Tytgat, C. R. Wildevuur and L. Eysman. Intestinal per- meability, circulating endotowin, and postoperative sys- temic responses in cardiac surgery patients. J. Cardiovasc. Vasc. Anesth, 10: 187-194 (1996).
[5] R. Schleiffer and F. Raul. Prophylactic administration of L-arginine improves the intestinal barrier function after mesenteric ischemia. Gut, 39: 194-198 (1996).
[6] A. L. Salzman, P. S. Wollert, H. Wang, M. J. Menconi, M. E. Youssef, C. C. Compton and M. P. Fink. Intralu- minal oxygenation ameliorates ischemia/reperfusion-in- duced gut mucosal hyperpermeability in pigs. Circ. Shock, 40: 37-46 (1993).
[7] A. L. Salzman, H. Wang, P. S. Wollert, T. J. Vandermeer, C. C. Compton, A. G. Denenberg and M. P. Fink. En- dotoxin-induced ileal mucosal hyperpermeability in pigs. Role of tissue acidosis. Am. J. Physiol., 266: G633-G646 (1994).
[8] J. L. Madara. Loosening tight junctions: lessons from the intestine. J. Clin. Invest, 83: 1089-1094 (1989).
[9] T. Sawada, T. Ogawa, M. Tomita, M. Hayashi and S. Awazu. Role of paracellular pathway in nonelectrolyte permeation across rat colon epithelium enhanced by so- dium caprate and sosium caprylate. Pharm. Res., 8: 1365- 1371 (1991).
[10] M. Tomita, Y. Hotta, R. Ohkubo, and S. Awazu. Polar- ized transport wa observed not in hydrophilic compounds but in dextran in Caco-2 cell monolayers. Biol. Pharm. Bull., 22: 330-331 (1999).
[11] M. Tomita, M. J. Menconi, R. L. Delude, and M. P. Fink. Polarized transport of hydrophilic compounds across rat colonic mucosa from serosa to mucosa is temperature dependent. Gastroenterol, 118: 535-543 (2000).
[12] A. Iida, M. Tomita, Y. Matsuura, Y. Takizawa and Ha- yashi, M. Improvement of Intestinal Absorption of P- glycoprotein Substrate by d-Tartaric Acid Drug Metab. and Pharmacokinet. 21(5): 424-428 (2006).
[13] J. T. Doluisio, N.F. Billups, E. T. Sugita and J. V. Swin- tosky, Drug absorption I: An in situ rat gut technique yielding realistic absorption rates. J. Pharm. Sci., 58: 1196-1202 (1969).
[14] M. Tomita, R. Ohkubo and M. Hayashi. Lipopolysaccharide transport system across colonic epithelial cells in normal and infective rat. Drug Metabol. Pharmacokin, 19 (1): 33-40 (2004).
[15] K. Sandvig and B. van Deurs. Selective modification of the endocytic uptake of eicin and fluid phase markers without alteration in transferring endocytosis. J. Biol. Chem., 265: 6382-6388 (1990).
[16] S. Wu-Pong, T. L. Weiss and C. A. Hunt. Antisense c- myc oligodeoxynucleotide cellular uptake. Pharm. Res., 9: 1010-1017 (1992).
[17] S. K. Rodal, G. Skretting, O. Garred, F. Vilhardt, B. van Deurs and K. Sandvig. Extraction of cholesterol with methyl-β-cyclodextrin perturbs formation of clathrin- coated endocytic vesicles. Mol. Biol. Cell, 10: 961-974 (1999).
[18] D. J. Falcone. Heparin stimulation of plasminogen acti- vator secretion by macrophage-like cell line RAW264.7: Role of the scavenger receptor. J. Cell Physiol., 140: 219- 226 (1989).
[19] L. Rohrer, M. Freeman, T. Kodama, M. Penman and M. Krieger. Coiled coli fibrous domains mediated ligand binding by macrophage scavenger receptor type II. Na- ture, 343: 570-572 (1990).
[20] B. L. Leu and J. D. Huang. Inhibition of intestinal P- glycoprotein and effect on etoposide absorption. Cancer Chemother. Pharmacol, 35: 432-436 (1995).
[21] G. Rappa, A. Lorico, R. A Flavell and A. C. Sartorelli. Evidence that the multidrug resistance protein (MRP) function as a co-transporter of glutathione and natural product toxins. Cancer Res., 57: 5232-5237 (1997).
[22] I. Tamai, A. Saheki, R. Saitoh, Y. Sai, I. Yamada and A. Tsuji. Nonlinear intestinal absorption og 5-hydroxytrip- tamine receptor antagonist caused by absorptive and sec- terory transporters. J. Pharmacol. Exp. Ther., 283: 108- 115 (1997).
[23] L. Z. Benet, C. Y. Wu, M. F. Hebert and V. J. Wachee. Intestinal drug metabolism and antiport processes: A po- tential paradigm I oral drug delivery. J. Contr. Rel., 39: 139-143 (1996).
[24] M. Tomita, M. Miwa, S. Ohuchi, T. Oda, J. Aketagawa, Y. Goto, and Masahiro Hayashi. Nonlinear intestinal ab- sorption of (1→3) β-D-glucan caused by absorptive and secretory transporting system. Biol. Pharm. Bull., 32: 1295-1297 (2009).
[25] Tomita, M., Menconi, M. J., Dekude, R. L. and Fink, M. P. Polarized transport of hydrophilic compounds across rat colonic mucosa from serosa to mucosa is temperature dependent. Gastroenterol, 118: 535-543 (2000).
[26] Goligorsky M. S. and Hruska, K. A. Transcytosis in cul- tured prpximal tubular cells. J. Membrane Biol., 93: 237- 247 (1986).
[27] Pantzar, N., Lundin, S. and Westrom, B. R. Bidirectional small-intestinal permeability in the rat to some common marker molecules in vitro. Scan. J. Gastroenterol., 29: 703-709 (1994).

  
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