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 [(125)I]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.
Western Australian Institute for Medical Research, B Block, Hospital Avenue, Nedlands, WA 6009, Australia.
Angela C
AC
D'Aprile
Lynette B
LB
Fernandes
Paul J
PJ
Rigby
Roy G
RG
Goldie
D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D002217:Carbachol; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D010224:Parainfluenza Virus 3, Human; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D010253:Respirovirus Infections / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; D002217:Carbachol; C072247:cyclo(Trp-Asp-Pro-Val-Leu)