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Opioid modulation of non‐cholinergic neural bronchoconstriction in guinea‐pig in vivo
Author(s) -
Belvisi M.G.,
Chung K.F.,
Jackson D.M.,
Barnes P.J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11661.x
Subject(s) - bronchoconstriction , cholinergic , guinea pig , in vivo , neuroscience , opioid , medicine , pharmacology , biology , endocrinology , asthma , receptor , microbiology and biotechnology
1 Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non‐cholinergic (NC) neural bronchoconstriction in guinea‐pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea‐pig. 2 Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea‐pigs which was reduced by atropine (1 mg kg −1 ), but the NC component was unaffected by hexamethonium (10 mg kg −1 ). 3 NC bronchoconstriction was reduced by morphine in a dose‐dependent manner (ED 50 = 132 μg kg −1 with a maximal inhibition of 79 ± 2.1% at 1 mg kg −1 ). Yohimbine (0.5 mg kg −1 ) did not alter the inhibitory effect of morphine (1 mg kg −1 ). 4 The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg −1 ) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg −1 ) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5 The selective μ‐opioid receptor agonist Tyr‐( d ‐Ala)‐Gly‐(N‐Me‐Phe)‐Glyol (DAGOL) was significantly more potent than morphine with an ED 50 of 5.4 μg kg −1 and complete inhibition at 100 μg kg −1 . The δ‐agonist Tyr‐( d ‐Pen)‐Gly‐Phe‐( d ‐Pen) (DPDPE) was less potent than DAGOL with an ED 50 of 28 μg kg −1 and a maximal inhibition of only 50 ± 5% at 100 μg kg −1 . The κ‐receptor agonist, U‐50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6 The bronchoconstrictor responses to exogenous substance P (25 μg kg −1 ) or acetylcholine (25 μg kg −1 ) were unaffected by morphine (500 μg kg −1 ). 7 We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on μ‐opioid receptors localized to sensory nerve endings in the airway.