ACETYLCHOLINE VIA MUSCARINIC RECEPTORS INHIBITS HISTAMINE-RELEASE FROM HUMAN ISOLATED BRONCHI

Human bronchi were incubated in organ baths to measure histamine relea se. The calcium ionophore A23187 (10 mu mol/L; 1 min) stimulated hista mine release by 148 +/- 28% (n = 11) above the prestimulation level bu t was ineffective in epithelium-denuded bronchi. Neither bradykinin (0 .1 mu mol/L) nor compound 48/80 (10 mu g/ml) triggered the release of histamine from epithelium-intact bronchi. Acetylcholine did not affect spontaneous histamine release (about 2 nmol/g x 5 min) but inhibited A23187-evoked histamine release in an atropine-sensitive manner. Alrea dy a concentration as low as 0.1 nmol/L acetylcholine was effective, t he maximal inhibition (by 89%) occurred at 100 nmol/L, whereas a conce ntration of 10 mu mol/L acetylcholine was ineffective. Oxotremorine (1 nmol/L), a stable agonist at muscarinic receptors, suppressed stimula ted histamine release completely. Physostigmine (0.1 mu mol/L), an ace tylcholinesterase inhibitor, reduced A23187-evoked histamine release b y 58%. Antihuman IgE antibody stimulated histamine release by 127 +/- 30% (n = 6) above the prestimulation level. Acetylcholine (100 nmol/L) inhibited also the immunologically evoked histamine release by 70%. I n conclusion, the present experiments provide a model to characterize mast cells that are localized in or close to the airway surface epithe lium. Acetylcholine via muscarinic receptors strongly inhibits the rel easability of these mucosal mast cells being among the first cells to interact with inhaled antigens and environmental agents. The inhibitor y action of physostigmine indicates the involvement of endogenous, pro bably non-neuronal acetylcholine expressed in airway epithelial cells.