Document Detail


Endothelin-A receptor-mediated prostanoid secretion via autocrine and deoxyribonucleic acid synthesis via paracrine signaling in human bronchial epithelial cells.
MedLine Citation:
PMID:  8895315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is known that serum promotes squamous differentiation of airway epithelial cell culture in vitro. We investigated which types of epithelial cells produce endothelins (ETs) and ET-evoked cellular responses in cultured human bronchial epithelial cells (HBECs). Squamous cells, not basal cells (nondifferentiated), secrete ET-1 actively. Specific binding of [125I]ET-1, not [125I]ET-3, was observed in squamous as well as basal cells, demonstrating the existence of only the ETA receptor. ET-1 together with epidermal growth factor stimulated synergistic DNA synthesis in basal cells, whereas ET-1 alone did not. Serum failed to induce DNA synthesis in HBECs, indicating terminal differentiation into squamous cells. ET-1 (1-100 nM) dose-dependently stimulated PGE2 (0.6-2.8 ng/10(5) cells) and thromboxane B2 release (4-30 pg/10(5) cells) from squamous HBECS, but not from basal cells. Western blot analysis showed that both squamous and basal HBECs expressed inducible and endothelial nitric oxide synthase, whereas ET-1 failed to stimulate nitric oxide synthase expression. Our findings suggest that secreted ET-1 from squamous cells evokes the release of prostanoids in an autocrine manner, and stimulates DNA synthesis in basal cells as a comitogen in a paracrine manner. Thus, it is likely that ET-1 secreted from HBECs plays an important role as a local, autocrine, and paracrine modulator in airway responses.
Authors:
M Takimoto; K Oda; Y Sasaki; T Okada
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Endocrinology     Volume:  137     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1996-12-17     Completed Date:  1996-12-17     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4542-50     Citation Subset:  AIM; IM    
Affiliation:
International Research Laboratories, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Azepines / pharmacology
Blood
Bronchi / cytology,  drug effects,  physiology*
Calcium / metabolism
Cells, Cultured
Culture Media
DNA / biosynthesis*
Endothelin-1 / biosynthesis,  pharmacology*,  physiology*
Endothelin-3 / metabolism
Epithelial Cells
Epithelium / drug effects,  physiology
Humans
Indoles / pharmacology
Isoenzymes / metabolism
Kinetics
Nitric Oxide Synthase / metabolism*
Nitrites / analysis
Prostaglandins / metabolism*
Receptor, Endothelin A
Receptors, Endothelin / physiology*
Signal Transduction* / drug effects
Substrate Specificity
Thymidine / metabolism
Chemical
Reg. No./Substance:
0/Azepines; 0/Culture Media; 0/Endothelin-1; 0/Endothelin-3; 0/Indoles; 0/Isoenzymes; 0/Nitrites; 0/Prostaglandins; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 142375-60-8/FR 139317; 50-89-5/Thymidine; 7440-70-2/Calcium; 9007-49-2/DNA; EC 1.14.13.39/Nitric Oxide Synthase

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