Evidence that pgf2[alpha]-induced contraction of isolated guinea -pig bronchi is mediated in part by release of tachykinins. Fujii, Kazuhiko, Hirotsugu Kohrogi, Hajime Iwagoe, Junji Hamamoto, Naomi Hirata, Tetsuro Yamaguchi, Osamu Kawano, and Masayuki Ando. First Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860 Japan
APStracts 2:0255A, 1995.
To investigate whether prostaglandin F2[alpha] (PGF2[alpha]) stimulates the release of tachykinins and whether the tachykinins play a role in the PGF2[alpha]-induced bronchial contraction, we examined the contractile response to PGF2[alpha] in the presence or absence of a neutral endopeptidase (NEP) inhibitor, phosphoramidon, in the guinea pig main bronchus in vitro. Because NEP effectively cleaves tachykinins, we hypothesized that the inhibition of NEP would enhance a PGF2[alpha]-induced bronchial contraction if PGF2[alpha] stimulates the release of tachykinins. Phosphoramidon significantly enhanced the concentration response curve to PGF2a. And it also significantly enhanced 10-5 M PGF2[alpha]-induced contraction. The enhancement was significantly attenuated in tissues where the tachykinins had been depleted by treatment with capsaicin. Furthermore, the enhancement of contraction was also significantly attenuated in the presence of tachykinin antagonist FK224 (10-5 M). Tetrodotoxin, a sodium channel blocker which blocks nerve conduction, did not affect the enhancement. From these results we conclude that 1) PGF2[alpha] causes the release of tachykinin-like substances, 2) these substances play a role in bronchial contraction in tissues where NEP activity is inhibited, and 3) nerve conduction is not necessary for the release of these substances in the guinea pig bronchus.

Received 28 December 1994; accepted in final form 6 June 1995.
APS Manuscript Number A1350-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.