The effect of the vasoactive intestinal polypeptide agonist Ro 25-1553 on induced tone in isolated human airways and pulmonary artery.
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.
Schmidt
D T
DT
Leiden University Medical Centre, Department of Pulmonology, Leiden, The Netherlands. D.Schmidt@lumc.nl
Rühlmann
E
E
Waldeck
B
B
Branscheid
D
D
Luts
A
A
Sundler
F
F
Rabe
K F
KF
D001980:Bronchi / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011651:Pulmonary Artery / Q000187:drug effects*; D011869:Radioligand Assay; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists* / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014018:Tissue Distribution; D014660:Vasoactive Intestinal Peptide / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology*
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide