PARAINFLUENZA VIRUS TYPE-3 INDUCED ALTERATIONS IN TACHYKININ NK1-RECEPTORS, SUBSTANCE-P LEVELS AND RESPIRATORY FUNCTIONS IN GUINEA-PIG AIRWAYS

We have investigated the effects of parainfluenza virus type 3 (PI-3) on sensory neuropeptide levels, tachykinin receptors and their functio ns in guinea pig airways during the course of respiratory viral infect ion. PI-3 infected guinea pigs were hyperresponsive to methacholine an d substance P aerosols as determined by earlier onset of dyspnea in th ese animals as compared with control on post-inoculation day (PID)7 bu t not 19. In addition, plasma protein extravasation produced in respon se to the tachykinin was increased in infected airways during the firs t week post inoculation. Infected guinea pig trachea did not respond a ny differently to methacholine when smooth muscle contraction and [H-3 ]inositol phosphate accumulation were measured although the magnitude of substance P effects using in vitro tests was significantly greater than control on post-inoculation day 7 but not 19. Trachea from PI-3 i nfected animals were characterized by reductions in substance P-like i mmunoreactivity, tachykinin NK1 receptor number and agonist affinity d uring the first post-inoculation week. Substance P levels or tachykini n NK1 receptor numbers or affinity were not altered in trachea of guin ea pigs 4 days after treatment with lipopolysaccharide. These data sug gest substance P release occurs during critical periods of respiratory viral infection which are temporally correlated with airway hyperresp onsiveness. Despite apparent down-regulation of tachykinin NK1 recepto rs, substance P-mediated functions remained enhanced suggesting some a lterations in post-receptor mechanisms.