Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically‐induced goblet cell secretion in guinea‐pig trachea

Goblet cell secretion in guinea‐pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea‐pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. Morphine, 1 mg kg⁻¹, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin‐sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin‐induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. Selective μ‐ or δ‐opioid receptor agonists, [d‐Ala², NMePhe⁴, Glyol⁵]enkephalin (DAMGO) or [d‐Pen², d‐Pen⁵]enkephalin (DPDPE) respectively, caused a dose‐related inhibition of low dose cigarette smoke‐induced goblet cell discharge, with DPDPE more potent than DAMGO. A κ‐receptor agonist, trans‐3,4‐dichloro‐N‐methyl‐N‐(2‐(1‐pyrollidinyl)cyclohexyl) benzeneacetamine (U‐50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. DAMGO dose‐dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 × 10⁻⁷ mol kg⁻¹. Neither DPDPE nor U‐50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO. We conclude that opioids inhibit neurally‐mediated goblet cell secretion via actions at prejunctional δ‐ and μ‐receptors on cholinergic nerves and at μ‐receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation. 1992 British Pharmacological Society