Putrescine and 5-hydroxytryptamine accumulation in rat lung slices: Cellular localization and responses to cell-specific lung injury*1

Nemery, Benoît; Ll, Smith; Wn, Aldridge

doi:10.1016/0041-008x(87)90198-0

Cited by 48 publications

(14 citation statements)

References 39 publications

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“…The cellular accumulation of a compound may be considered as occurring via an active process when the accumulation: (i) occurs against a concentration gradient; (ii) is energy dependent; (iii) obeys saturation kinetics; and (iv) shows structure specificity. The pulmonary uptake of putrescine and other polyamines has been shown to fulfil these criteria when normal lung tissue or pulmonary epithelial cells from animals or humans were studied (Smith et al, 1982;Nemery et al, 1987;Hoet et al, 1993;. None of these requirements appeared to be met in the present study in which pulmonary tumoral tissue was examined: (i) There was no evidence for accumulation of putrescine against a concentration gradient in the neoplastic tissue (Figure 2).…”

Section: Discussionmentioning

confidence: 49%

“…The site of this uptake has been convincingly demonstrated to be essentially made up by the alveolar epithelium, i.e. type I and type II pneumocytes, as shown by autoradiography in both animal and human lungs (Nemery et al, 1987;Wyatt et al, 1988;Dinsdale et al, 1991;Hoet et al, 1993). In addition, the non-ciliated bronchiolar (Clara) cells of the rat are also a site of uptake, at least in vitro (Nemery et al, 1987;Wyatt et al, 1988), but this could neither be confirmed or denied for the human lung (Hoet et al, 1993).…”

mentioning

confidence: 99%

“…type I and type II pneumocytes, as shown by autoradiography in both animal and human lungs (Nemery et al, 1987;Wyatt et al, 1988;Dinsdale et al, 1991;Hoet et al, 1993). In addition, the non-ciliated bronchiolar (Clara) cells of the rat are also a site of uptake, at least in vitro (Nemery et al, 1987;Wyatt et al, 1988), but this could neither be confirmed or denied for the human lung (Hoet et al, 1993). Neither the alveolar cells nor the Clara cells are characterised by a high proliferation rate in the normal lung (Kauffman, 1980), and thus the reasons for the substantial accumulation of polyamines by lung tissue are still unclear.…”

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confidence: 99%

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Putrescine accumulation in human pulmonary tumours

Hoet

Dinsdale²,

Verbeken³

et al. 1996

Br J Cancer

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Summary Type 11 pneumocytes and Clara cells, both epithelial cells that possess an active uptake system for polyamines, have been identified as possible precursor cells of at least some types of lung tumours. In this study we have investigated whether human pulmonary tumours exhibit putrescine uptake. Lung slices from both tumoral tissue and non-tumoral tissue, obtained from patients undergoing surgery for lung cancer, were incubated with radiolabelled putrescine at both 37C and 4'C. The accumulation of putrescine was evaluated by its apparent kinetic parameters, in the presence or absence of cystamine, and by autoradiography. The investigated tumoral tissue (six squamous carcinomas and five adenocarcinomas) did not show accumulation of putrescine above that attributable to simple diffusion, except for one adenocarcinoma. In this specimen autoradiography showed that the accumulation was not specifically associated with any particular cell type, but that practically every cell accumulated putrescine. We conclude that human pulmonary tumours do not accumulate polyamines in a manner similar to normal pulmonary epithelial cells.

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Section: Discussionmentioning

confidence: 49%

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confidence: 99%

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confidence: 99%

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Putrescine accumulation in human pulmonary tumours

Hoet

Dinsdale²,

Verbeken³

et al. 1996

Br J Cancer

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“…The alveolar Type H ceUs are also specifically labeled and there is diffuse label on or near the alveolar Type I epithelial cells. It is not possible with the resolution ofthe light microscope to be categoric that this cell type has accumulated the polyamines (14,15). However, since the Type I cell is damaged with paraquat and there is an absence of labeling in the vascular endothelium lining the larger blood vessels, it seems reasonable to conclude this cell also accumulates putrescine and, by analogy, paraquat (15).…”

Section: Location Of the Uptake System In The Lungmentioning

confidence: 96%

“…The first report to use autoradiographic techniques to visualize the compartment indicated that tritiated paraquat was confined almost entirely to cells having the typical distribution of alveolar Type II cells (13). Recently, it has been shown that in lung slices incubated with tritiated putrescine, spermidine, or spermine the label is concentrated in Clara cells, whereas adjacent ciliated cells remain almost entirely unlabeled (14,15). The alveolar Type H ceUs are also specifically labeled and there is diffuse label on or near the alveolar Type I epithelial cells.…”

Section: Location Of the Uptake System In The Lungmentioning

confidence: 99%

The Importance of Epithelial Uptake Systems in Lung Toxicity

Smith¹,

Lewis²,

Wyatt³

et al. 1990

Environmental Health Perspectives

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The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization ofthe process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell.With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells.In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system. IntroductionBecause the lung is responsible for all gas exchange necessary for oxidative metabolism, it is inevitably exposed to toxic gases, vapors, and particles (if small enough) present in the atmosphere. The respiratory function of the lung requires a large surface area (in man, about the size of a tennis court) that, on the air side, is covered by epithelial cells intimately associated with an extensive capillary network. Apart from inhalation, the lung is also exposed to toxic compounds that have been absorbed into the bloodstream or are in the form of metabolites, formed either in the lung or in extrapulmonary tissue.In order to meet its respiratory function, the lung requires numerous cell types. More than 40 cell types have been identified in the lung (1); these are required to provide the diverse architecture associated with cartilage, smooth muscle, connective tissue, submucosal glands, the vascular system, and the respiratory unit (alveoli)

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Respiratory and non‐respiratory lung function indices during the development and resolution of O,S,S‐trimethyl phosphorodithioate‐induced lung damage in the rat. A chemical model of adult respiratory distress syndrome

Nemery

1987

J of Applied Toxicology

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Arterial blood gases and the pulmonary uptake of putrescine and 5-hydroxytryptamine (5-HT) were studied between 6 h and 18 days after the administration to rats of an oral LD50-dose of the pneumotoxin, O,S,S-trimethyl phophorodithioate (OSSMe), a potential impurity in several organophosphorus insecticides. Aortic blood was sampled under pentobarbitone anaesthesia for measurements of arterial pH, and partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). PaO2 was significantly decreased 4 days after OSSMe administration, i.e. at the time of maximum lethality and increases in wet lung weight. This was accompanied by a significant increase in PaCO2 and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear, PaCO2 was slightly increased 2, 6 and 12 days after dosing. The uptake of putrescine (1,4-diaminobutane) and of 5-HT was measured by incubating lung slices with several concentrations of [3H]-putrescine and [14C]-5-HT, so as to estimate the apparent kinetic parameters of uptake, Vmax and Km. The Vmax for putrescine-uptake was significantly decreased 1, 2, 4, 6 and 12 days after the administration of OSSMe. The Vmax for 5-HT-uptake was significantly increased 1 day and significantly decreased 4 days after OSSMe administration. The uptake of 5-HT is an endothelial function, and the decrease in 5-HT-uptake at 4 days may reflect injury to the pulmonary vascular endothelium at this time. The uptake of putrescine probably reflects the function of the pulmonary (mainly alveolar) epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

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Putrescine and 5-hydroxytryptamine accumulation in rat lung slices: Cellular localization and responses to cell-specific lung injury*1

Cited by 48 publications

References 39 publications

Putrescine accumulation in human pulmonary tumours

Putrescine accumulation in human pulmonary tumours

The Importance of Epithelial Uptake Systems in Lung Toxicity

Respiratory and non‐respiratory lung function indices during the development and resolution of O,S,S‐trimethyl phosphorodithioate‐induced lung damage in the rat. A chemical model of adult respiratory distress syndrome

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