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Effect of respiratory tract viral infection on murine airway β‐adrenoceptor function, distribution and density
Author(s) -
Henry Peter J.,
Rigby Paul J.,
Mackenzie John S.,
Goldie Roy G.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12526.x
Subject(s) - respiratory tract , respiratory system , lung , biology , virus , medicine , endocrinology , immunology , anatomy
1 The effects of a respiratory tract viral infection on β‐adrenoceptor density, distribution and function were investigated in murine airways. 2 Following intranasal inoculation of CBA/CaH mice with influenza A/PR‐8/34 virus, the virus proliferated rapidly in trachea (peak titres 2 days post‐inoculation) and lung (peak titres 4–6 days post‐inoculation). Respiratory tract viral infection was associated with a significant increase in lung weight (88% higher than control mice at day 6 post‐inoculation) that was related temporally to the development of peripheral lung inflammation and consolidation. 3 Analysis of specific binding of [ 125 I]‐cyanopindolol to β‐adrenoceptors revealed that on days 2, 4 and 8 post‐inoculation with virus, mouse isolated tracheal sections contained, on average, 40% more β‐adrenoceptors than tracheal sections from time matched control mice. Subsequent quantitative autoradiographic studies demonstrated that this increase in total tracheal β‐adrenoceptors was due primarily to a 90% increase in the density of β‐adrenoceptors in the tracheal epithelium in virus‐infected mice. 4 In contrast, virus‐infection had no significant effect on the density of β‐adrenoceptors in tracheal airway smooth muscle, although within 2 days of inoculation with virus, mouse tracheal smooth muscle segments were approximately 2 fold less sensitive to the β‐adrenoceptor agonist, noradrenaline (mean pD 2 = 6.57 ± 0.04, n = 24) and to the adenylyl cyclase‐activator forskolin (mean pD 2 = 6.78 ± 0.04, n = 12) compared to segments from control mice (mean pD 2 = 6.84 ± 0.06 for noradrenaline; mean pD 2 = 7.03 ± 0.07 for forskolin). Similar values were obtained 8 days post‐inoculation. At day 2, but not day 8 post‐inoculation with virus, relaxation responses to theophylline were also marginally attenuated compared with controls. 5 Mouse isolated tracheal segments obtained 2 days after virus inoculation and segments from time‐matched control mice were equisensitive to the spasmogenic actions of the muscarinic cholinoceptor agonist, carbachol. However, tracheal segments from mice inoculated with virus were less responsive to carbachol on day 4 (mean pD 2 = 6.45 ± 0.04, n = 8) and day 8 (mean pD 2 = 6.45 ± 0.02, n = 12) compared to control preparations (day 4, mean pD 2 = 6.73 ± 0.06, n = 8; day 8, mean pD 2 = 6.65 ± 0.04, n = 12, P < 0.05). In contrast, endothelin‐1‐induced contractions of tracheal smooth muscle were not affected by virus‐infection. 6 These data demonstrate that respiratory tract viral infection can produce significant tissue‐selective changes in airway β‐adrenoceptor density as well as small reductions in airway smooth muscle muscarinic cholinoceptor and β‐adrenoceptor function.