Muscarinic stimulation of prostanoid synthesis by the isolated rat trachea: calcium dependency and effect of cortisol and cigarette smoke

Tracheal prostanoid synthesis was stimulated by parasympathomimetics: arecoline > carbachol = methacholine > acetylcholine ≫ arecaidine. McNA343, dimethyl phenyl piperazinium (DMPP), nicotine, potassium and isoprenaline were without effect. Prostanoid synthesis was also stimulated by Ca²⁺ ionophore A23187 and arachidonic acid (AA). Carbachol-stimulated prostanoid synthesis was inhibited antagonists (atropin > ipratropium bromide ≫ gallamine > pirenzepine); adrenaline and isoprenaline were without effect. Carbachol-stimulated prostanoid synthesis was also inhibited by the Ca²⁺-channel blockers, nifedipine, diethylstilboestrol and TMB-8. Hydrocortisone and betamethasone inhibited carbachol- and A23187-stimulated, but not AA-stimulated, prostanoid synthesis following an 18 h tissue culture. Cigarette smoke extracts had a biphasic effect on carbachol-, A23187- and AA-stimulated prostanoid synthesis (potentiation at low concentrations, inhibition at high concentrations of extracts). These data demonstrate (1) that rat tracheal prostanoid synthesis is stimulable by activation of muscarine receptor-linked Ca²⁺ mobilisation, and (2) that tracheal prostanoid synthesis may be involved in secretion of mucus, the disruption of which by cigarette smoking may be related to the pathophysiology of airway disease.