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Cited by 269

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 access
Döring, F, Walter, J, Will, J, Föcking, M, Boll, M, Amasheh, S, Clauss, W, Daniel, H·1998·Journal of Clinical Investigation

Abstract

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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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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CoChat. (2026). Citation check: Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. https://app.cochat.ai/papers/10.1172/jci1909
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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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