An autoradiographic study of δ-aminolevulinic acid uptake by mouse brain

Terr, Leonid I.; Weiner, Leslie P.

doi:10.1016/0014-4886(83)90234-0

Cited by 36 publications

(21 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies, applying in situ hybridization of mRNA distribution of PEPT2 in rabbit and human brain, show that the message abundance is restricted to neuronal cells and the epithelium of the choroid plexus (31). This distribution matches again with the observation that autoradiography performed in brain tissues after in vitro administration of radiolabeled ALA in rats showed uptake of ALA into the brain only in restricted areas such as the choroid plexus but not at the blood brain barrier nor into the neuronal tissue (32). In contrast, isolated neurons in primary culture were capable of accumulating ALA and, subsequently, also porphyrins when ALA was provided in the culture medium (33).…”

Section: Discussionsupporting

confidence: 87%

Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.

Döring¹,

Walter²,

Will³

et al. 1998

J. Clin. Invest.

257

182

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 87%

Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.

Döring¹,

Walter²,

Will³

et al. 1998

J. Clin. Invest.

257

182

View full text Add to dashboard Cite

show abstract

“…In the case of 5‐ALA, no active transport was identified so far and the diffusion from blood to normal brain tissue is very low . There is significantly more uptake from blood in the choroid plexus, resulting in some uptake into the cerebrospinal fluid, but still leading to much lower 5‐ALA concentrations than circulating in the blood plasma . Overall, with the exception of the ependymal lining, normal brain is very well protected from 5‐ALA and hence photosensitization.…”

Section: ‐Ala—fundamentalsmentioning

confidence: 98%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

View full text Add to dashboard Cite

Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

show abstract

“…E. Smith, Johanson, and Keep 2004). Reabsorptive transport from CSF is essential because ALA leaks into CSF from blood and needs to be quickly cleared from the ventricles (arrow 10, Figure 1) to avoid toxicity (Terr and Weiner 1983).…”

Section: Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

et al. 2010

View full text Add to dashboard Cite

Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway (''nexus'') of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance.

show abstract

An autoradiographic study of δ-aminolevulinic acid uptake by mouse brain

Cited by 36 publications

References 11 publications

Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.

Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.

5‐ALA in the management of malignant glioma

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

Contact Info

Product

Resources

About