Effect of respiratory tract viral infection on murine airway β‐adrenoceptor function, distribution and density

Abstract

The effects of a respiratory tract viral infection on β‐adrenoceptor density, distribution and function were investigated in murine airways. 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. Analysis of specific binding of [125I]‐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. 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 pD2 = 6.57 ± 0.04, n = 24) and to the adenylyl cyclase‐activator forskolin (mean pD2 = 6.78 ± 0.04, n = 12) compared to segments from control mice (mean pD2 = 6.84 ± 0.06 for noradrenaline; mean pD2 = 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. 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 pD2 = 6.45 ± 0.04, n = 8) and day 8 (mean pD2 = 6.45 ± 0.02, n = 12) compared to control preparations (day 4, mean pD2 = 6.73 ± 0.06, n = 8; day 8, mean pD2 = 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. 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.

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

“…Changes in the histological appearance of tracheal tissue associated with parainfluenza-1 virus infection in rats and mice seen in this study were similar to those described previously (Robinson et al, 1968;Massion et al, 1993) and were similar to changes observed in other animal models of respiratory tract viral infections (Buckner et al, 1985;Henry et al, 1991). These included marked alterations in the structure of the epithelial cell layer and cellular infiltration into the submucosal layer of the trachea that were apparent at day 4 post-inoculation in both species.…”

Influence of Influenza A Infection on Capsaicin-Induced Responses in Murine Airways

“…Influenza A virus infection has been associated with reduced relaxation responses in airway smooth muscle (Henry et al, 1991;Ashraf et al, 2001). However, virus-induced reductions in relaxation responses were observed only for capsaicin and SP, which cause relaxation indirectly via the release of COX products such as PGE 2 .…”

“…Second, certain neurotrophic influenza A strains can infect the central nervous system via the sensory nervous system (Shinya et al, 2000), and this may affect sensory nerve function. Finally, influenza A infection can alter the density, distribution, and function of an array of receptors involved in controlling bronchomotor tone (Henry et al, 1991;Carr et al, 1996;Lan et al, 2004). This study tested the hypothesis that influenza A infection inhibits the capsaicin-induced relaxation pathway by altering sensory nerve, epithelial cell, and smooth muscle function.…”

ETB but not ETA receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

“…respiratory autonomic nervous system by inhibiting the func-tion of neuronal M2 muscarinic autoreceptors and thereby increasing the release of acetylcholine from parasympathetic nerves (Fryer & Jacoby, 1991) and by inhibiting P-adrenoceptor function in airway smooth muscle and inflammatory cells (Lee, 1980;Henry et al, 1991). Endothelin-1 is a 21 amino acid peptide synthesized within and released from several cell types, including airway epithelial cells (MacCumber et al, 1989;Black et al, 1989;Rozengurt et al, 1990).…”