Prejunctional control of pH 6-induced bronchoconstriction by NK1, NK2, mu-opioid, alpha(2)-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 c ompletely abolished after systemic pretreatment with capsaicin. Pretreatmen t with the NK2 receptor antagonist SR 48968 (5 x 10(-7) M) completely inhib ited bronchoconstriction and significantly reduced the immunoreactivity ind uced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 x 10(-7) M) and, t o 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-li ke immunoreactivity overflow. The effects of morphine and UK14304 were part ially 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 re ceptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-l ike immunoreactivity and bronchoconstriction.