Acetylcholine via muscarinic receptors inhibits histamine release from human isolated bronchi.
Human bronchi were incubated in organ baths to measure histamine release. The calcium ionophore A23187 (10 mumol/L; 1 min) stimulated histamine release by 148 +/- 28% (n = 11) above the prestimulation level but was ineffective in epithelium-denuded bronchi. Neither bradykinin (0.1 mumol/L) nor compound 48/80 (10 micrograms/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. Already a concentration as low as 0.1 nmol/L acetylcholine was effective, the maximal inhibition (by 89%) occurred at 100 nmol/L, whereas a concentration of 10 mumol/L acetylcholine was ineffective. Oxotremorine (1 nmol/L), a stable agonist at muscarinic receptors, suppressed stimulated histamine release completely. Physostigmine (0.1 mumol/L), an acetylcholinesterase inhibitor, reduced A23187-evoked histamine release by 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%. In conclusion, the present experiments provide a model to characterize mast cells that are localized in or close to the airway surface epithelium. Acetylcholine via muscarinic receptors strongly inhibits the releasability of these mucosal mast cells being among the first cells to interact with inhaled antigens and environmental agents. The inhibitory action of physostigmine indicates the involvement of endogenous, probably non-neuronal acetylcholine expressed in airway epithelial cells.
Reinheimer
T
T
Department of Pharmacology, University of Mainz, Academic St. Hildegardis Hospital, Germany.
Baumgärtner
D
D
Höhle
K D
KD
Racké
K
K
Wessler
I
I
D000109:Acetylcholine / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D046508:Culture Techniques / Q000379:methods; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006636:Histamine Release / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D007476:Ionophores; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C049425:oxotremorine sesquifumarate; D007073:Immunoglobulin E; D000001:Calcimycin; D010095:Oxotremorine; D001285:Atropine; D010830:Physostigmine; D000109:Acetylcholine