Impact of parainfluenza-3 virus infection on endothelin receptor density and function in guinea pig airways

We examined the impact of parainfluenza-3 (P-3) respiratory tract viral infection on the density and function of endothelin (ET) receptor subtypes (ET_A and ET_B) in guinea pig tracheal smooth muscle. Total specific binding of [¹²⁵I]ET-1 and the relative proportions of ET_A and ET_B binding sites for this ligand were assessed at day 0 (control) and at 2, 4, 8 and 16 days post-inoculation. At day 0, the proportions of ET_A and ET_B binding sites were 30% and 70% respectively. Total specific binding was significantly reduced at day 4 post-inoculation (32% reduction, n = 8–12, P<0.05) and was largely due to a corresponding fall in ET_B receptor density at this time point (38% reduction, n = 8–12, P<0.05). The density of ET_A receptors also fell significantly at day 8 post-inoculation (33% reduction, n = 6–12, P<0.05). By day 16 post-inoculation, the densities of ET_A and ET_B receptors had recovered to control values. The ratio of ET_A:ET_B receptor subtypes did not alter with P-3 infection. While P-3 infection reduced the density of tracheal smooth muscle ET_A and ET_B receptors, the contractile sensitivity and maximum response to carbachol and ET-1 was not altered in tissue from day 4 post-inoculation compared with the control. There seems to be a significant functional reserve for both receptor subtypes in this species that buffers the impact of P-3 infection on airway smooth muscle responsiveness to ET-1.