Opioid modulation of non‐cholinergic neural bronchoconstriction in guinea‐pig in vivo

Abstract

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 (ED₅₀ = 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 ED₅₀ 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 ED₅₀ 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.