AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 6 1066-L1069, Copyright © 1997 by American Physiological Society
PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs
H. Kanazawa, H. Kamoi, T. Kawaguchi, S. Shoji, T. Fujii, S. Kudoh, K. Hirata and J. Yoshikawa
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified
hypotensive peptide, may play physiological roles in airway and
cardiovascular controls. This study was designed to determine the mechanism
responsible for the bronchoprotective effects of PAMP on capsaicin-induced
bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M)
significantly inhibited capsaicin-induced bronchoconstriction in a
dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was
as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The
concentration of immunoreactive substance P (SP) in bronchoalveolar lavage
fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10
fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a
dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84
+/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for
10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect
exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction,
whereas isoproterenol (10(-7) M) significantly inhibited exogenous
tachykinin-induced bronchoconstriction. These findings suggest that the
bronchoprotective effects of PAMP are mainly due to inhibition of the
release of tachykinins at airway C-fiber endings.
