BRONCHODILATATION BY TACHYKININS AND CAPSAICIN IN THE MOUSE MAIN BRONCHUS

1 The effect of sensory neuropeptides and capsaicin on basal and stimulated tone of mouse bronchial smooth muscle has been evaluated. 2 In basal conditions neither sensory neuropeptides (substance P, neurokinin A or calcitonin gene-related peptide (CGRP) nor capsaicin exerted any contractile effects. However, when a tonic contraction was induced with carbachol (1-mu-M) a prompt relaxation was induced by substance P (1- 100 nM) and by neurokinin A (1- 100 nM), with substance P being more potent. A second application of substance P was without effect. CGRP (10 nM) produced only a very small and erratic relaxation. Relaxation was also induced by capsaicin (1-mu-M), and this response could be evoked only once in each preparation. In 4 out of 6 preparations a cross-desensitization between substance P and capsaicin was observed. 3 The selective NK1 tachykinin agonist, [Pro9]-SP sulphone (1-mu-M), exerted potent bronchodilator actions on carbachol-contracted mouse bronchial preparations. In contrast, neither [beta-Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a concentration of 1-mu-M), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects. Furthermore, the selective NK1 tachykinin antagonist, (+/-)-CP 96,345 (1-mu-M), abolished substance P (1 nM)- but not isoprenaline (0.1-mu-M)-induced relaxations. 4 Application of electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s) to carbachol-contracted preparations evoked a transient contraction followed by a relaxation. The tetrodotoxin-sensitive slow component of this relaxation was reduced following capsaicin desensitization. 5 In the presence of indomethacin (5-mu-M) the relaxation induced by substance P, capsaicin or EFS was suppressed. 6 In conclusion, the mouse main bronchus appears to be a monoreceptorial tissue containing only NK1 receptors which subserve bronchodilator functions. Such receptors could be activated by exogenous or endogenously (capsaicin or EFS) released tachykinins and the consequent relaxation is probably mediated by the generation of prostanoids.