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The endothelins in the pulmonary system
R G Goldie1, P G Knott, M J Carr
1Department of Pharmacology, University of Western Australia, Perth, Nedlands, Australia.
Pulmonary Pharmacology
|April 1, 1996
Summary
Endothelin peptides (ETs) impact the respiratory system, with ET-1 synthesized in the lung. Research explores their role in pulmonary diseases like hypertension and asthma, with future studies focusing on receptor antagonists and inhibitors.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Molecular Biology
Background:
- Endothelin peptides (ETs) initially studied for cardiovascular effects are now recognized for broad respiratory functions.
- Endothelin-1 (ET-1) is actively synthesized, stored, released, and metabolized within the lung, indicating its physiological and pathophysiological relevance.
- Two ET receptor subtypes, ETA and ETB, are confirmed in the lung, mediating airway smooth muscle contraction and proliferation.
Purpose of the Study:
- To review the established and potential roles of endothelin peptides in respiratory system function and disease.
- To highlight the current understanding and future research directions regarding ETs in pulmonary conditions, particularly asthma and pulmonary hypertension.
Main Methods:
- Literature review of existing research on endothelin peptides and their receptors in the respiratory system.
- Analysis of studies investigating ET-1's effects on airway smooth muscle, nerves, and inflammatory cells.
- Discussion of preliminary data and future research needs, including clinical evaluation of receptor antagonists.
Main Results:
- ETs exhibit significant activities in the respiratory tract, with ET-1 playing a key role in lung physiology and pathology.
- Pulmonary hypertension shows the most convincing association with ETs, while their role in asthma is still under investigation.
- Research has primarily focused on ET-1's bronchoconstrictor effects, with emerging interest in its impact on nerves and inflammatory cells.
Conclusions:
- Endothelin peptides are implicated in various pulmonary diseases, though causal links require further substantiation.
- Future research should focus on ET effects on neural and inflammatory components in asthma and chronic airway exposure.
- Clinical trials using selective ET receptor antagonists and inhibitors of endothelin-converting enzymes (ECE-1, ECE-2) are crucial for validating the pathophysiological roles of ETs and developing therapeutics.