Abstract

In anesthetized, artificially ventilated rabbits not treated with thiorphan (2 mg/kg), a neutral endopeptidase (NEP) inhibitor, substance P (SP) and neurokinin A (NKA) in doses from 0.2 to 2.7 μg/kg produced dose-related increases in rapidly adapting pulmonary stretch receptor (RAR) activity without any significant changes in total lung resistance (R_L), whereas neurokinin B (NKB) at the same concentrations did not significantly alter either RAR activity or R_L. In comparison with the excitatory responses of RAR activity to SP and NKA, the magnitudes of increased receptor activity evoked SP were significantly larger than those after NKA administration. The rank order of tachykinins for RAR stimulus potency was SP > NKA > KB. Pretreatment with thiorphan potentiated the increases of RAR activity and R_L induced by SP but had no effect on the RAR and R_L responses to NKA and NKB. Subsequent administration of L 659, 877 (a selective NK₂ receptor antagonist, 2.3 and 7.6 μg/kg) that dose-dependently inhibited NKA-induced RAR stimulation did not significantly influence augmentation of the RAR and R_L responses to SP. Administration of atropine (2 mg/kg,n = 6) in thiorphan-treated rabbits, which had no effect on NKA- and NKB-induced RAR stimuli, significantly attenuated the increases of RAR activity and R_L induced by SP. These results suggest that tachykinin-induced RAR stimulation is mediated by the activation of NK₂ receptors, probably involving participation of NK₁ receptors. Furthermore, potentiation of the increases of RAR activity and R_L produced by SP administration in the presence of thiorphan is partly mediated by facilitation of cholinergic neurotransmission.