Abstract
Background Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties. Methods Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists. Results Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a β2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high-dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells. Conclusions This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors.
Highlights
Anaphylaxis is a severe allergic reaction and a potentially life-threatening acute multisystem syndrome caused by the sudden release of mast cell-derived mediators [1]
Mast cells preincubated with relatively higher doses of adrenaline (100 μM, 1 mM; Figure 1(a), E and F) did not show such findings characteristic of exocytosis
Since 1 μM prazosin inhibited the process of exocytosis in mast cells (Figure 6(a)), we examined its effect on the adrenaline-induced inhibition of exocytosis (Figure 7)
Summary
Anaphylaxis is a severe allergic reaction and a potentially life-threatening acute multisystem syndrome caused by the sudden release of mast cell-derived mediators [1]. To determine the effects of adrenaline or α-adrenergic receptor agonists/antagonists on the stabilization of mast cells, previous in vitro studies measured the drug-induced changes in histamine release from mast cells [6, 9,10,11]. They were not enough to monitor the whole process of exocytosis, since mast cells release fibrogenic factors, growth factors and inflammatory cytokines in addition to chemical mediators [12]. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors
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