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ET Receptor-Linked Signal Transduction Processes in the Airway Wall

  • Chapter
Pulmonary Actions of the Endothelins

Part of the book series: Respiratory Pharmacology and Pharmacotherapy ((RPP))

  • 43 Accesses

Abstract

The vascular endothelium and airway epithelium are well-documented cellular sources of ET-1. The release of ET-1 from epithelial cells appears to be towards the submucosal surface and into the airway wall, since the ET-1 content of the basal side of airway epithelial cells is many fold higher than that of the apical side [1]. Due to its close proximity to the airway epithelium, the underlying airway smooth muscle is likely to be an important target within the airway wall for epithelium-derived ET-1. Additional studies [2], which have assessed the topographical location of vascular endothelial cells and the ability of these cells to generate ET-1, suggest that endothelium cell-derived ET-1 might also exert significant effects on airway smooth muscle. The induction of a strong and long-lasting contraction is the most extensively studied action of ET-1 on airway smooth muscle, although it has been reported to bring about other actions including relaxation and mitogenesis. Furthermore, ET-1 significantly affects the functions of other important structures within the airway wall, causing microvascular leakage and oedema, potentiation of cholinergic nerve-mediated contraction, stimulation of mucous gland secretion, as well as exerting wide-ranging effects on the airway epithelium [3]. Each of these effects is produced via the interaction of ET-1 with specific ET receptors and the activation of regulatory G proteins and intracellular signal transduction processes. Interestingly, recent studies suggest that ET-1, via ET receptors, can activate a wide range of quite different signal transduction pathways. By way of illustration, ET-1 has been shown in many cell types to stimulate the phosphoinositide pathway leading to the release of intracellular calcium, as well as to promote the influx of extracellular calcium through plasma membrane channels. In other instances, the signal transduction pathway activated by ET-1 has been shown to involve enzyme systems (e.g., protein kinase C, phospholipase A2, phospholipase D, protein tyrosine kinase, adenylate cyclase and guanylate cyclase), ion transporters (e.g., Na+-H+ exchange) and ion channels (e.g., chloride channels). This chapter provides an overview of our current, albeit incomplete, understanding of the signal transduction processes which link ET receptors to cellular responses in the airway wall.

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  1. Department of Pharmacology, University of Western Australia, Stirling Hwy., 6907, Nedlands, Western Australia, Australia

    Peter J. Henry

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  1. Faculty of Medicine & Dentistry Department of Pharmacology, University of Western Australia, Perth Nedlands, WA, 6907, Australia

    Roy G. Goldie

  2. Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, 19406-0939, USA

    Douglas W. P. Hay

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Henry, P.J. (1999). ET Receptor-Linked Signal Transduction Processes in the Airway Wall. In: Goldie, R.G., Hay, D.W.P. (eds) Pulmonary Actions of the Endothelins. Respiratory Pharmacology and Pharmacotherapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8821-9_5

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  • DOI: https://doi.org/10.1007/978-3-0348-8821-9_5

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-5859-4

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