Muscarinic Control of Histamine Release from Airways Inhibitory M1-receptors in Human Bronchi but Absence in Rat Trachea

Isolated human bronchi and rat tracheae were incubated in organ baths to measure histamine release. The calcium ionophore A23187, 3 μ mol/L in rat trachea and 10 μ mol/L in human bronchi, stimulated histamine release by 145 ± 50% (n = 6) and 270 ± 48% (n = 7) above the prestimulation level, respectively. Acetylcholine (100 pmol/L; human bronchi) or oxotremorine (1, 100, 10,000 nmol/L; rat trachea) did not affect the spontaneous histamine release. In rat tracheae neither acetylcholine nor oxotremorine inhibited A23187-evoked histamine release, whereas 100 pmol/L acetylcholine significantly suppressed the evoked histamine release in human bronchi by 86%. For receptor characterization the following subtype-specific muscarinic receptor antagonists were applied: pirenzepine (M1 subtype), para-fluorohexahydrosiladifendiol (pFHHSiD; similar affinities at human cloned M1-, M3-, and M4-receptors), AF-DX 116 (M2 subtype), and clozapine (antagonist at cloned M1-, M2-, M3-receptors; agonist at cloned M4-receptors). P...