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

To investigate whether prostaglandin F-2 alpha (PGF(2 alpha)) stimulat es the release of tachykinins and whether the tachykinins play a role in the PGF(alpha 2)-induced bronchial contraction, we examined the con tractile response to PGF(2 alpha) in the presence or absence of a neut ral endopeptidase (NEP) inhibitor phosphoramidon in the guinea pig mai n bronchus in vitro. Because NEP effectively cleaves tachykinins, we h ypothesized that the inhibition of NEP would enhance a PGF(2 alpha)-in duced bronchial contraction if PGF(2 alpha) stimulates the release of tachykinins. Phosphoramidon significantly enhanced the concentration-r esponse curve to PGF(2 alpha). And it also significantly enhanced 10(- 5) M PGF(2 alpha)-induced contraction. The enhancement was significant ly attenuated in tissues where the tachykinins had been depleted by tr eatment with capsaicin. Furthermore, the enhancement of contraction wa s also significantly attenuated in the presence of tachykinin antagoni st FK-224 (10(-5) M). Tetrodotoxin, a sodium-channel blocker that bloc ks nerve conduction, did not affect the enhancement. From these result s we conclude that 1) PGF(2 alpha) causes the release of tachykinin-li ke substances, 2) these substances play a role in bronchial contractio n 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.