EVIDENCE THAT PGF(2-ALPHA)-INDUCED CONTRACTION OF ISOLATED GUINEA-PIG BRONCHI IS MEDIATED IN PART BY RELEASE OF TACHYKININS

To investigate whether prostaglandin F-2 alpha (PGF(2 alpha)) stimulates the release of tachykinins and whether the tachykinins play a role in the PGF(alpha 2)-induced bronchial contraction, we examined the contractile response to PGF(2 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 PGF(2 alpha)-induced bronchial contraction if PGF(2 alpha) stimulates the release of tachykinins. Phosphoramidon significantly enhanced the concentration-response curve to PGF(2 alpha). And it also significantly enhanced 10(-5) M PGF(2 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) PGF(2 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.