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The effect of the vasoactive intestinal polypeptide agonist Ro 25-1553 on induced tone in isolated human airways and pulmonary artery

Schmidt, D; Ruhlmann, E; Waldeck, B; Branscheid, D; Luts, A; Sundler, Frank LU and Rabe, K F (2001) In Naunyn-Schmiedeberg's Archives of Pharmacology 364(4). p.314-320
Abstract
Ro 25-1553 is a metabolically stable analogue of endogenous vasoactive intestinal polypeptide (VIP). This compound is a potent bronchodilator in vitro as well as in vivo. Moreover, Ro 25-1553 has been shown to be highly selective of the VPAC2 receptor. We assessed the effect of Ro 25-1553 on isolated human bronchi and pulmonary arteries in vitro. Macroscopically normal human airways and pulmonary arteries were obtained from patients undergoing surgery for lung cancer. The relaxing capability of Ro 25-1553 on bronchial and pulmonary artery tone was measured using standard techniques. Bronchial rings were pre-contracted with 0.1 mM histamine, and tone in pulmonary artery rings was induced with 10 microM PGF2alpha. Increasing concentrations... (More)
Ro 25-1553 is a metabolically stable analogue of endogenous vasoactive intestinal polypeptide (VIP). This compound is a potent bronchodilator in vitro as well as in vivo. Moreover, Ro 25-1553 has been shown to be highly selective of the VPAC2 receptor. We assessed the effect of Ro 25-1553 on isolated human bronchi and pulmonary arteries in vitro. Macroscopically normal human airways and pulmonary arteries were obtained from patients undergoing surgery for lung cancer. The relaxing capability of Ro 25-1553 on bronchial and pulmonary artery tone was measured using standard techniques. Bronchial rings were pre-contracted with 0.1 mM histamine, and tone in pulmonary artery rings was induced with 10 microM PGF2alpha. Increasing concentrations of Ro 25-1553 within a range of 1 pM to 10 microM were added and isometric tension changes were recorded. Ro 25-1553 caused a concentration-dependent relaxation of airway and pulmonary artery preparations, with an EC50 of approximately 10 nM and a maximal relaxation of 70%-75% of the induced tone. The presence of VPAC2 receptors in the two tissues, though low in density, was confirmed by in situ hybridization, immunocytochemistry and ligand binding. These findings indicate that the VIP analogue Ro 25-1553 may be useful in the treatment of asthma and/or chronic obstructive pulmonary diseases. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Human pulmonary artery, Human bronchus, Smooth muscle relaxation, VPAC 2 receptor, Ro 25-1553, VIP
in
Naunyn-Schmiedeberg's Archives of Pharmacology
volume
364
issue
4
pages
314 - 320
publisher
Springer
external identifiers
  • pmid:11683518
  • scopus:0034784746
ISSN
0028-1298
DOI
10.1007/s002100100458
language
English
LU publication?
yes
id
59bc6dd9-b5be-4545-bfa2-532fbf337bee (old id 1120359)
date added to LUP
2008-08-27 13:21:02
date last changed
2018-01-07 05:37:23
@article{59bc6dd9-b5be-4545-bfa2-532fbf337bee,
  abstract     = {Ro 25-1553 is a metabolically stable analogue of endogenous vasoactive intestinal polypeptide (VIP). This compound is a potent bronchodilator in vitro as well as in vivo. Moreover, Ro 25-1553 has been shown to be highly selective of the VPAC2 receptor. We assessed the effect of Ro 25-1553 on isolated human bronchi and pulmonary arteries in vitro. Macroscopically normal human airways and pulmonary arteries were obtained from patients undergoing surgery for lung cancer. The relaxing capability of Ro 25-1553 on bronchial and pulmonary artery tone was measured using standard techniques. Bronchial rings were pre-contracted with 0.1 mM histamine, and tone in pulmonary artery rings was induced with 10 microM PGF2alpha. Increasing concentrations of Ro 25-1553 within a range of 1 pM to 10 microM were added and isometric tension changes were recorded. Ro 25-1553 caused a concentration-dependent relaxation of airway and pulmonary artery preparations, with an EC50 of approximately 10 nM and a maximal relaxation of 70%-75% of the induced tone. The presence of VPAC2 receptors in the two tissues, though low in density, was confirmed by in situ hybridization, immunocytochemistry and ligand binding. These findings indicate that the VIP analogue Ro 25-1553 may be useful in the treatment of asthma and/or chronic obstructive pulmonary diseases.},
  author       = {Schmidt, D and Ruhlmann, E and Waldeck, B and Branscheid, D and Luts, A and Sundler, Frank and Rabe, K F},
  issn         = {0028-1298},
  keyword      = {Human pulmonary artery,Human bronchus,Smooth muscle relaxation,VPAC 2 receptor,Ro 25-1553,VIP},
  language     = {eng},
  number       = {4},
  pages        = {314--320},
  publisher    = {Springer},
  series       = {Naunyn-Schmiedeberg's Archives of Pharmacology},
  title        = {The effect of the vasoactive intestinal polypeptide agonist Ro 25-1553 on induced tone in isolated human airways and pulmonary artery},
  url          = {http://dx.doi.org/10.1007/s002100100458},
  volume       = {364},
  year         = {2001},
}