The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.
Open accessAbstract
Delta-aminolevulinic acid (ALA) is the precursor of porphyrin synthesis and has been recently used in vitro and in clinical studies as an endogenous photosensitizer for photodynamic therapy in the treatment of various tumors. For this purpose, ALA is given topically, systemically, or orally. When administered by the oral route, it shows excellent intestinal absorption. ALA is also efficiently reabsorbed in the renal proximal tubule after glomerular filtration. However, the pathways and mechanisms for its transmembrane transport into epithelial cells of intestine and kidney are unknown. Here we demonstrate that ALA uses the intestinal and renal apical peptide transporters for entering into epithelial cells. Kinetics and characteristics of ALA transport were determined in Xenopus laevis ooyctes and Pichia pastoris yeast cells expressing either the cloned intestinal peptide transporter PEPT1 or the renal form PEPT2. By using radiolabeled ALA and electrophysiological techniques in these heterologous expression systems, we established that: (a) PEPT1 and PEPT2 translocate 3H-ALA by saturable and pH-dependent transport mechanisms, (b) that ALA and di-/tripeptides, but not GABA or related amino acids, compete at the same substrate-binding site of the carriers, and (c) that ALA transport is electrogenic in nature as a consequence of H+/ALA cotransport. Reverse transcriptase-PCR analysis performed with specific primers for PEPT1 and PEPT2 in rabbit tissues demonstrates that, in particular, the PEPT2 mRNA is expressed in a variety of other tissues including lung, brain, and mammary gland, which have been shown to accumulate ALA. This suggests that these tissues could take up the porphyrin precusor via expressed peptide transporters, providing the endogenous photosensitizers for efficient photodynamic therapy.
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Cites
Expression cloning of a mammalian proton-coupled oligopeptide transporter
Fei, Y.-J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F. H., Romero, M. F., Singh, S. K., Boron, W. F., & Hediger, M. A. (1994) · Nature · doi:10.1038/368563a0 · Cited by 891
Human Intestinal H+/Peptide Cotransporter
Liang, R., Fei, Y.-J., Prasad, P. D., Ramamoorthy, S., Han, H., Yang-Feng, T. L., Hediger, M. A., Ganapathy, V., & Leibach, F. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6456 · Cited by 502
Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy
Loh, C., MacRobert, A., Bedwell, J., Regula, J., Krasner, N., & Bown, S. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.284 · Cited by 263
Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney
Liu, W., Liang, R., Ramamoorthy, S., Fei, Y.-J., Ganapathy, M. E., Hediger, M. A., Ganapathy, V., & Leibach, F. H. (1995) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(95)80036-f · Cited by 260
The PTR family: a new group of peptide transporters
Steiner, H., Naider, F., & Becker, J. M. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.tb02310.x · Cited by 243
Saito, H., Okuda, M., Terada, T., Sasaki, S., & Inui, K. (1995) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12227-1 · Cited by 242
MOLECULAR BIOLOGY OF MAMMALIAN AMINO ACID TRANSPORTERS
Malandro, M. S., & Kilberg, M. S. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.001513 · Cited by 210
Boll, M., Herget, M., Wagener, M., Weber, W. M., Markovich, D., Biber, J., Clauss, W., Murer, H., & Daniel, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.284 · Cited by 192
Self-citationBoll, M., Markovich, D., Weber, W. M., Korte, H., Daniel, H., & Murer, H. (1994) · Pflügers Archiv European Journal of Physiology · doi:10.1007/bf02584043 · Cited by 191
Self-citationMechanisms of the Human Intestinal H+-coupled Oligopeptide Transporter hPEPT1
Mackenzie, B., Loo, D. D. F., Fei, Y.-J., Liu, W., Ganapathy, V., Leibach, F. H., & Wright, E. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5430 · Cited by 160
Cited by
Transport of Milk Constituents by the Mammary Gland
Shennan, D. B., & Peaker, M. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.925 · Cited by 411
Contribution of microbial amino acids to amino acid homeostasis of the host
Metges, C. C. (2000) · The Journal of Nutrition · doi:10.1093/jn/130.7.1857s · Cited by 391
5‐Aminolevulinic Acid Derivatives in Photomedicine: Characteristics, Application and Perspectives
Fotinos, N., Campo, M. A., Popowycz, F., Gurny, R., & Lange, N. (2006) · Photochemistry and Photobiology · doi:10.1562/2006-02-03-ir-794 · Cited by 238
Transport of 5-aminolevulinic acid between blood and brain
Ennis, S. R., Novotny, A., Xiang, J., Shakui, P., Masada, T., Stummer, W., Smith, D. E., & Keep, R. F. (2003) · Brain Research · doi:10.1016/s0006-8993(02)03749-6 · Cited by 146
Kitajima, Y., Ishii, T., Kohda, T., Ishizuka, M., Yamazaki, K., Nishimura, Y., Tanaka, T., Dan, S., & Nakajima, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-44981-y · Cited by 56
Metadata
- Authors
- Döring, F., Walter, J., Will, J., Föcking, M., Boll, M., Amasheh, S., Clauss, W., & Daniel, H.
- Venue
- Journal of Clinical Investigation
- Published
- 1998-06-15
- Volume
- 101
- Issue
- 12
- Pages
- 2761-2767
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1992404214
- Cited by
- 269
- References
- 29
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Döring, F., Walter, J., Will, J., Föcking, M., Boll, M., Amasheh, S., Clauss, W., & Daniel, H. (1998). Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. Journal of Clinical Investigation. https://doi.org/10.1172/jci1909
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