Journal of Applied Physiology, Vol 71, Issue 2 452-457, Copyright © 1991 by American Physiological Society
Relative bronchoconstrictor activity of neurokinin A and neurokinin A fragments in guinea pigs
S. A. Shore and J. M. Drazen
Respiratory Biology Program, Harvard School of Public Health, Boston, Massachusetts.
We examined the effect of rapid intravenous infusion of neurokinin A (NKA)
and selected COOH-terminal NKA fragments on pulmonary conductance (GL) and
dynamic compliance in anesthetized mechanically ventilated guinea pigs. The
rank order of the dose of peptide required to reduce GL by 50% (ED50GL) was
NKA = NKA2-10 = NKA3-10 = NKA4-10 less than NKA5-10 much less than NKA6-10.
The time course of bronchoconstriction induced by NKA2-10, NKA3-10, and
NKA4-10 was similar to that induced by NKA, whereas NKA5-10 and NKA6-10
each had a shorter duration of action than NKA for a similar induced
maximal change in GL. To determine whether degradation of these NKA
fragments by neutral endopeptidase (NEP) modulates their bronchoconstrictor
activity as it does for native NKA, we examined the effect of the NEP
inhibitor SCH32615 on NKA3-10-, NKA5-10-, and NKA6-10-induced changes in
GL. We have previously reported that the ED50GL for NKA was approximately
20-fold lower in animals pretreated with SCH32615 (1 mg/kg) than in control
guinea pigs. SCH32615 caused a 16-fold decrease in ED50GL for NKA3-10 (P
less than 0.001) but had no effect on airway responses to NKA5-10 or
NKA6-10. The results demonstrate that the magnitude and duration of
bronchoconstriction induced by potential aminopeptidase degradation
products of NKA are similar to those of the native peptide. Aminopeptidases
do not, therefore, have the capacity to modulate the bronchoconstriction
induced by this peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
