Postjunctional inhibitory effect of the NK2 receptor antagonist, SR 48968, on sensory NANC bronchoconstriction in the guinea-pig.
1 The effects of a selective NK2 receptor antagonist, SR 48968, on non-adrenergic non-cholinergic (NANC) bronchoconstriction in the guinea-pig were investigated in both in vitro and in vivo studies. 2 In isolated bronchus, the electrical field stimulation (EFS, 1 Hz for 1 min)-induced NANC bronchoconstriction was inhibited by 83% after preincubation with SR 48968 (10(-7) M) for 1 h. The selective NK1 receptor antagonist, CP 96,345 (10(-6) M), together with SR 48968 completely abolished the remaining EFS-evoked NANC bronchial contraction. ST 48968 (10(-7) M) totally blocked the bronchial contraction caused by neurokinin A (NKA), but reduced only slightly the bronchoconstriction caused by high concentrations of substance P (SP) and did not influence the response to acetylcholine (ACh). 3 In the guinea-pig isolated perfused lung, SR 48968 (5 x 10(-7) M) perfusion for 30 min markedly reduced, by 95% and 68% respectively, the increase in lung resistance (RL) and the decrease in dynamic compliance (CDyn) evoked by vagal stimulation (1 Hz for 1 min). Capsaicin (10(-8) M)-evoked bronchoconstriction was also significantly inhibited by SR 48968 (5 x 10(-7) M). However, the same concentration of SR 48968 did not affect the release of neuropeptide calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) evoked by either vagal stimulation or capsaicin in the isolated perfused lung, suggesting no prejunctional action.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Postjunctional inhibitory effect of the NK2 receptor antagonist, SR 48968, on sensory NANC bronchoconstriction in the guinea-pig. Lou, Y.P., Lee, L.Y., Satoh, H., Lundberg, J.M. Br. J. Pharmacol. (1993) [Pubmed]
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