The impact of respiratory syncytial virus infection on endothelin receptor function and release in sheep bronchial explants.
We investigated the impact of respiratory syncytial virus (RSV) infection, an important asthma precipitant, on endothelin receptor function and release in sheep bronchial explants. RSV infection was confirmed using polymerase chain reaction and immunohistochemistry. Since sheep airway smooth muscle contains only endothelin-A receptors, sarafotoxin (Stx) S6c did not cause airway contraction. In contrast, sarafotoxin S6c (300 nM) caused contraction in RSV-infected bronchial explants (8 +/- 3% carbachol Emax). However, we could not detect airway smooth muscle endothelin-B receptors in explants using autoradiography. RSV infection per se did not alter the release of immunoreactive endothelin from sheep bronchial explants (control = 11.6 +/- 0.9 pg versus RSV = 12.1 +/- 0.9 pg). Interestingly, dexamethasone (1 microM) alone increased endothelin release in both control (17.9 +/- 2.0 pg) and RSV-infected tissue (18.3 +/- 3.1 pg). The combined presence of protease-activated receptor-2 (PAR-2) ligand (100 microM) and dexamethasone (1 microM) also increased endothelin release from control tissue (17.3 +/- 1.4 pg), but endothelin release was suppressed by PAR-2 ligand in RSV-infected tissue (10.3 +/- 0.8 pg), probably because PAR-2 expression was increased by RSV. In summary, the novel expression of endothelin-B receptors triggered by RSV might be relevant to RSV-associated asthma. Furthermore, activation of airway PAR-2 may be protective in asthma where endothelin levels are elevated in part via endothelin release suppression.
Fernandes
Lynette B
LB
Pharmacology Unit, School of Medicine & Pharmacology, The University of Western Australia and Western Australian Institute for Medical Research, Perth, Western Australia, Australia. lfernandes@pharm.uwa.edu.au
D'Aprile
Angela C
AC
Self
Glenn J
GJ
Harnett
Gerald B
GB
Goldie
Roy G
RG
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D017077:Culture Media, Conditioned / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism* / Q000503:physiopathology; D012756:Sheep; D013997:Time Factors; D046509:Tissue Culture Techniques; D014757:Viper Venoms / Q000494:pharmacology
D017077:Culture Media, Conditioned; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D044464:Receptor, PAR-2; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788; D003907:Dexamethasone; D015232:Dinoprostone; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D007213:Indomethacin