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Contractile endothelin-B (ETB) receptors in human small bronchi

Adner, Mikael LU ; Cardell, Lars-Olaf LU ; Sjöberg, Trygve LU ; Ottosson, A and Edvinsson, Lars LU (1996) In European Respiratory Journal 9(2). p.351-355
Abstract
Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from... (More)
Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Respiratory Journal
volume
9
issue
2
pages
351 - 355
publisher
Eur Respiratory Soc
external identifiers
  • pmid:8777976
  • scopus:0030060653
ISSN
1399-3003
DOI
10.1183/09031936.96.09020351
language
English
LU publication?
yes
id
0fd95fd0-0192-4ef6-a7c1-d29f86367340 (old id 1111112)
date added to LUP
2008-07-21 08:34:56
date last changed
2017-01-01 04:57:16
@article{0fd95fd0-0192-4ef6-a7c1-d29f86367340,
  abstract     = {Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.},
  author       = {Adner, Mikael and Cardell, Lars-Olaf and Sjöberg, Trygve and Ottosson, A and Edvinsson, Lars},
  issn         = {1399-3003},
  language     = {eng},
  number       = {2},
  pages        = {351--355},
  publisher    = {Eur Respiratory Soc},
  series       = {European Respiratory Journal},
  title        = {Contractile endothelin-B (ETB) receptors in human small bronchi},
  url          = {http://dx.doi.org/10.1183/09031936.96.09020351},
  volume       = {9},
  year         = {1996},
}