Substance P antagonists and the role of tachykinins in non-cholinergic bronchoconstriction

摘要: Electrical field stimulation of guinea-pig isolated hilus bronchi induced tetrodotoxin-sensitive contractions which only a minor part could be inhibited by atropine. The remaining non-cholinergic bronchonstriction was antagonized heptapeptide and an undecapeptide substance P (SP) analogue (Arg5, D-Trp7, 9) SP5–11, IC50 = 24.0 μM (D-Pro2, 9)SP, 10.0 μM. Of the exogenously added tachykinins, both eledoisin (8 times) physalaemin (3 were more potent bronchoconstrictors than SP. Pretreatment with SP-analogues shifted concentration-response curves to tachykinins right, being most readily antagonized. 9)SP5–11 also neural response that In addition, in frog sciatic nerve preparation two found possess lidocaine-like neurodepressant actions further complicated interpretation inhibitory effects these compounds. It is concluded if tachykinin contributes bronchoconstriction, eledoisin-like peptide likely candidate SP itself. Since SP-antagonists may have local anaesthetic properties their value as tools neurophysiology seems limited. Inferentially, bronchoconstrictive neurotransmitter remains identified.