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This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/L185    most recent 00167.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Pan, J. Articles by Cutz, E. Search for Related Content PubMed PubMed Citation Articles by Pan, J. Articles by Cutz, E.

Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development

¹Division of Pathology, Department of Pediatric Laboratory Medicine, ²Canadian Institutes of Health Research Lung Group, ³The Research Institute, The Hospital for Sick Children, and ⁴Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Submitted 14 April 2005 ; accepted in final form 9 August 2005

Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (PO₂ 20 mmHg), stretch-induced 5-HT release was not affected by Ca²⁺-free medium or nifedipine (50 µM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid (5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

mechanosensitive ion channels; amine storage pools; neuroendocrine cell secretion; hypoxia-induced secretion; fetal lung fluid

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