Functional characterization of L-tryptophan transport across mammalian cornea

Authors

  • Mahendra Singh Rathore B R Nahata College of Pharmacy, (Affiliated to Rajiv Gandhi Prodhyogiki Vishwavidhylalaya, Bhopal, MP) P B 06, Mhow Neemuch Road, Mandsaur, MP 458001 India
  • Vipin Bihari Gupta B R Nahata College of Pharmacy, (Affiliated to Rajiv Gandhi Prodhyogiki Vishwavidhylalaya, Bhopal, MP) P B 06, Mhow Neemuch Road, Mandsaur, MP 458001 India

Keywords:

Cornea, Amino acid, Tryptophan, Transport

Abstract

In last few years transporter targeted drug delivery has drawn attention of research to identify and explore various nutrient transport systems including amino acid transporters for better drug delivery. The aim of present research work is to investigate the transport characteristics of L-tryptophan (L-try) across goat cornea. Transport of L-try was investigated using a glass diffusion cell for effect of concentration, pH, presence of other amino acids or metabolic inhibitor or dipeptide and tripeptide. The amount of L-try transported increased as the pH of L-try aqueous solution increased from 5 to 9. Inhibition was observed in L-try transport in absence of sodium ions where L-try solution was made isotonic with dextrose. Amino acids like L-histidine, L-arginine, L-lysine (cationic), L-glutamic acid, L-aspartic acid (anionic), glycine and L-proline (neutral) inhibited the L-try transport as compared to control (L-try alone). In presence of sodium azide and Ouabain the inhibition in L-try transport across goat cornea was observed while no marked inhibition was observed on L-try transport across goat cornea in presence of aspartame and glutathione. The L-try transport was favored up to concentration 1% w/v and at higher pH in presence of sodium ions through excised goat cornea. Functional presence of a sodium dependent L-try transport system as inhibited by ouabain having affinity to cationic and neutral amino acid is evident on goat cornea.

References

Christensen H.N. Role of amino acid transport

and counter transport in nutrition and metabolism.

Physiol Rev. 1990;70:43-77.

Christensen H.N., Albritton L.M., Kakuda D.K.

Gene-product designations for amino acid

transporters. J Exp Biol. 1994;196:51-57.

Broer S., Wagner C.A., Lang F. Function and

structure of heterodimeric amino acid

transporters. Am J Physiol. 2001;281:C1077-

C109.

Palacin M., Estevez R., Bertran J. Molecular

biology of mammalian plasma membrane amino

acid transporters. Physiol Rev. 1998;78:969-1054.

Deves R., Boyd C.A. Transporters for cationic

amino acids in animal cells: discovery, structure,

and function. Physiol Rev. 1998;78:487-545.

Kekuda R., Torres Z.V., Fei Y.J. Molecular and

functional characterization of intestinal Na+-

dependent neutral amino acid transporter B0. Am

J Physiol.1997;272:G1463-G1472.

Torrents D., Estevez R., Pineda M. Identification

and characterization of a membrane protein (y+L

amino acid transporter-1) that associates with

F2hc to encode the amino acid transport activity

y

+L: a candidate gene for lysinuric protein

intolerance. J Biol Chem. 1998;273:32437-32445.

Pfeiffer R., Rossier G., Spindler B. Amino acid

transport of y+L-type by heterodimers of

F2hc/CD98 and members of the glycoproteinassociated amino acid transporter family. EMBO

J. 1999;18:49-57.

Anand B.S., Mitra A.K. Mechanism of corneal

permeation of L-valyl ester of acyclovir: targeting

the oligopeptide transporter on the rabbit cornea.

Pharm Res. 2002;19:1194-1202.

Jain V.B., Pal D.,Gunda S.,Nashed Y.,Ganapathy

V., Mitra A.K. identification of a Na+-dependent

cationic and neutral amino acid transporter,B 0,+ in

human and rabbit cornea. Mol Pharm.

;1:338-346.

Anand B.S., Katragadda S., Nashed Y.E., Mitra

A.K. Amino acid prodrugs of acyclovir as

possible antiviral agents against ocular HSV-1

infections: interactions with the neutral and

cationic amino acid transporter on the corneal

epithelium. Curr Eye Res. 2004;29:153-66.;

Majumdar S., Nashed Y.E, Patel K., Jain R.,

Itahashi M., Neumann D.M., Hill J.M., Mitra

A.K. Dipeptide monoester ganciclovir prodrugs

for treating HSV-1-induced corneal epithelial and

stromal keratitis: in vitro and in vivo evaluations.

J Ocul Pharmacol Ther. 2005;21:463-74.

Nielsen C.U., Vabeno J., Andersen R., Brodin B.,

Steffansen B. Recent advances in therapeutic

applications of human peptide transporters. Expert

Opin Ther Patents. 2005;15:153–166.

Niederkorn J.Y., Meyer D.R., Ubelaker J.E.,

Martin J.H. Ultrastructural and

immunohistological characterization of the SIRC

corneal cell line. In Vitro Cell Dev Biol. 1990;

:923–930.

Carl G.F., Hoffman W.H., Blankenship P.R.,

Litaker M.S., Hoffman M.G., Mabe P.A. Diabetic

Ketoacidosis depletes plasma tryptophan. Endocr

Res. 2002;28:91-102.

Vrensen G.F., Van M.J., Jonges R., Voorhout W.,

Breipohl W., Wegener A.R. Tryptophan

deficiency arrests chromatin breakdown in

secondary lens fibers of rats. Exp Eye Res.

;78:661-672.

Rathore M.S., Majumdar D.K. Effect of

Formulation Factors on In Vitro Transcorneal

Permeation of Gatifloxacin From Aqueous Drops.

AAPS PharmSciTech. 2006; 7: E1-E6.

Downloads

Published

2010-09-30

How to Cite

Mahendra Singh Rathore, & Vipin Bihari Gupta. (2010). Functional characterization of L-tryptophan transport across mammalian cornea. International Journal of Drug Delivery, 2(3), 251–257. Retrieved from https://ijdd.arjournals.org/index.php/ijdd/article/view/37

Issue

Section

Original Research Articles