Evidence that PGF2 alpha-induced contraction of isolated guinea pig bronchi is mediated in part by release of tachykinins.
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 PGF2 alpha. 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 FK-224 (10(-5) M). Tetrodotoxin, a sodium-channel blocker that 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.
Fujii
K
K
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Kohrogi
H
H
Iwagoe
H
H
Hamamoto
J
J
Hirata
N
N
Yamaguchi
T
T
Kawano
O
O
Ando
M
M
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D015237:Dinoprost / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D006020:Glycopeptides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D015320:Tachykinins; C075570:FK 224; D013779:Tetrodotoxin; D015237:Dinoprost; D002211:Capsaicin; C008890:phosphoramidon