Prejunctional Control of pH 6-Induced Bronchoconstriction by NK1, NK2, μ-Opioid, α2-Adrenoceptor and Glucocorticoid Receptors in Guinea-pig Isolated Perfused Lung

This study investigated the release of calcitonin‐gene related peptide‐like (CGRP) immunoreactivity and bronchoconstriction induced by pH 6 buffer in guinea‐pig isolated perfused lung. Both pH 6‐induced CGRP‐like immunoreactivity and bronchoconstriction were completely abolished after systemic pretreatment with capsaicin. Pretreatment with the NK2 receptor antagonist SR 48968 (5 times 10−7M) completely inhibited bronchoconstriction and significantly reduced the immunoreactivity induced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 times 10−7M) and, to a lesser extent the NK1 antagonist CP 96345, morphine (5 times 10−6M), the α2‐adrenoceptor agonist UK 14304 (10−7M) and betamethasone (10−6M) significantly reduced both pH 6‐induced bronchial response and CGRP‐like immunoreactivity overflow. The effects of morphine and UK14304 were partially reversed by naloxone (5 times 10−5M) and idazoxan (5 times 10−5M). Therefore, NK1, NK2, μ‐opioid, α2‐adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer‐induced CGRP‐like immunoreactivity and bronchoconstriction.