Influence of parainfluenza‐1 respiratory tract viral infection on endothelin receptor‐effector systems in mouse and rat tracheal smooth muscle

• Published in: British journal of pharmacology 1996-09, Vol.119 (2), p.291-298
• Main Authors: Knott, Patrick G., Henry, Peter J., McWilliam, Andrew S., Rigby, Paul J., Fernandes, Lynette B., Goldie, Roy G.
• Format: Article
• Language: English
• Subjects: Animal viral diseases; Animals; Biological and medical sciences; Endothelin Receptor Antagonists; Endothelin receptors; Endothelin-1 - pharmacology; In Vitro Techniques; Infectious diseases; Male; Medical sciences; Methacholine Chloride - pharmacology; Mice; Mice, Inbred CBA; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - ultrastructure; Parainfluenza Virus 1, Human; parainfluenza‐1 virus; Peptides, Cyclic - pharmacology; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin - metabolism; Receptors, Endothelin - physiology; Respiratory Tract Infections - physiopathology; Respiratory Tract Infections - virology; Respirovirus Infections - physiopathology; Respirovirus Infections - virology; sendai virus; Time Factors; Trachea - ultrastructure; tracheal smooth muscle; Vasoconstrictor Agents - pharmacology; Viper Venoms - pharmacology; Viral diseases
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15984.x

1 In this study we have compared the effects of parainfluenza‐1 respiratory tract viral infection on the density and function of ETA and ETB receptors in rat and mouse tracheal airway smooth muscle. 2 The bronchoconstrictor effect of inhaled methacholine was significantly enhanced in virus‐infected rats, at both 4 and 12 days post‐inoculation. That is, the concentration of methacholine causing an increase in resistance of 100% (PC100 methacholine) was significantly lower in virus‐infected animals at both 4 and 12 days post‐inoculation (n = 6–8; P < 0.05). 3 Total specific binding of [125I]‐endothelin‐1 and the relative proportions of ETA and ETB binding sites for [125I]‐endothelin‐1 were assessed in tracheal airway smooth muscle in parainfluenza‐1‐infected rats and mice at days 2, 4 and 12 post‐inoculation using the ligands BQ‐123 (1 μm; ETA receptor‐selective) and sarafotoxin S6c (100 nM; ETB receptor‐selective). Total specific binding in mice was significantly reduced at day 2 post‐inoculation (n = 5; P < 0.05) but not at days 4 and 12 post‐inoculation (n = 5). In control mice, the proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day 4 and these were significantly altered by parainfluenza‐1 infection such that, the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post‐inoculation, the proportion of ETA and ETB binding sites in tracheal smooth muscle from mice infected with parainfluenza‐1 was not significantly different from control. In rat tracheal airway smooth muscle, neither total specific binding nor the ETA and ETB binding site ratio (64%:36%) were significantly altered in virus‐inoculated rats at days 2, 4 or 12 post‐inoculation (n = 5). 4 Parainfluenza‐1 infection in mice had no effect on the sensitivity or maximal contractile effect of endothelin‐1 in tracheal smooth muscle at days 2, 4 or 12 post‐inoculation (n = 4). In contrast, contraction in response to the ETB receptor‐selective agonist sarafotoxin S6c was attenuated by 39% at day 2 and by 93% at day 4 post‐inoculation (P < 0.05). However, by day 12 post‐inoculation, contractions to sarafotoxin S6c were not significantly different between control and virus‐infected mice. In parainfluenza‐1‐infected rats, there were small but significant reductions in the sensitivity to carbachol, endothelin‐1 and sarafotoxin S6c whilst the maximal responses to the highest concentrations of these agonists were not significantly altered by virus infection (n