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 x 10(-7) M) completely inhibited bronchoconstriction and significantly reduced the immunoreactivity induced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 x 10(-7) M) and, to a lesser extent the NK1 antagonist CP 96345, morphine (5 x 10(-6) M), the alpha(2)-adrenoceptor agonist UK 14304 (10(-7) M) and betamethasone (10(-6) M) 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 x 10(-5) M) and idazoxan (5 x 10(-5) M). Therefore, NK1, NK2, mu-opioid, alpha(2)-adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-like immunoreactivity and bronchoconstriction.