Prejunctional control of pH 6-induced bronchoconstriction by NK1, NK2, mu-opioid, alpha2-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 alpha2-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(-50M). Therefore, NK1, NK2, mu-opioid, alpha2-adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-like immunoreactivity and bronchoconstriction.
Auberson
S
S
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lacroix
J S
JS
Kordestani
R K
RK
Lundberg
J M
JM
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D016084:Bronchoconstriction / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism
D058647:Adrenergic alpha-2 Receptor Agonists; D001549:Benzamides; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011810:Quinoxalines; D011812:Quinuclidines; D018341:Receptors, Adrenergic, alpha-2; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid; D018041:Receptors, Neurokinin-2; D017450:Receptors, Opioid, mu; C085215:SR 140333; D000068438:Brimonidine Tartrate; C073839:SR 48968; D009020:Morphine; D001623:Betamethasone; D015740:Calcitonin Gene-Related Peptide; C066892:CP 96345