Tachykinin recovery during postmortem bronchoconstriction in guinea pig lungs.
We examined the role of substance P (SP) and neurokinin A (NKA) in the postmortem bronchoconstriction in guinea pig lungs using isolated lungs superfused via the trachea. Airway opening pressure (Pao) during superfusion was monitored and the superfusate collected for analysis of SP- and NKA-like immunoreactivities (SP-LI and NKA-LI, respectively). Peak Pao (39.0 +/- 3.9 cmH2O) was reached 10 min after starting superfusion; Pao decreased slowly thereafter, reaching only 9.9 +/- 2.2% of the peak value 2 h after starting superfusion (P less than 0.005); 12.6 +/- 2.6 and 34.0 +/- 9.7 fmol of SP-LI and NKA-LI, respectively, were found in the fraction corresponding to 10-20 min of superfusion. Recovered immunoreactivities decreased to 5.2 +/- 0.3 and 9.3 +/- 1.8 fmol of SP-LI and NKA-LI, respectively, in the fraction corresponding to 110-120 min of superfusion (P less than 0.05). Inhibition of neutral endopeptidase with thiorphan resulted in significantly greater increases in Pao (P less than 0.005) and augmentation of the recovery of SP-LI and NKA-LI (P less than 0.05 and P less than 0.001, respectively). Capsaicin treatment of animals 7-10 days before the removal of their lungs abolished the increase in Pao during superfusion and resulted in a significant decrease in the amount of SP-LI and NKA-LI recovered. Our data confirm that tachykinin release occurs during postmortem bronchoconstriction in guinea pig lungs and, furthermore, that tachykinin degradation by NEP modulates the intensity of this response.
Martins
M A
MA
Departments of Medicine, Beth Israel Hospital, Brigham and Women's Hospital, Boston, Massachusetts.
Shore
S A
SA
Drazen
J M
JM
D000818:Animals; D001980:Bronchi / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D015260:Neprilysin / Q000502:physiology; D015288:Neurokinin A / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D013373:Substance P / Q000378:metabolism*
D013373:Substance P; D015288:Neurokinin A; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin