EFFECTS OF SR-48968 ON THE NEUROPEPTIDE GAMMA-INDUCED CONTRACTION OF THE HUMAN ISOLATED BRONCHUS

Neuropeptide gamma (NP gamma) induced a contractile response of the human isolated bronchus which was potentiated by the neutral endopeptidase inhibitor, phosphoramidon, but was not modified by atropine and indomethacin. NP gamma was 3.31-fold more potent than NKA. Contractile response curves to NP gamma were shifted to the right and maximal responses reduced by the non-peptide NK2-receptor antagonist, SR 48968. The pK(B) of SR 48968 (8.94 +/- 0.18, n = 15), calculated according to Kenakin (1987) was very close to that reported for [Nle(1O)]-NKA (4-10), a specific agonist of neurokinin NK2-receptors (8.86 +/- 0.13, n = 13), suggesting that the contractile effects of NP gamma on the human isolated bronchus were mediated through NK2A-receptors.