What question did this study set out to answer?

To compare the effects of olodaterol and formoterol on histamine release and β2-adrenoceptor desensitisation in human lung mast cells and airway smooth muscle cells.

March 17, 2026

A comparison of β 2 -adrenoceptor desensitisation induced by olodaterol and formoterol in human lung mast cells and airway smooth muscle cells

Key Points

To compare the effects of olodaterol and formoterol on histamine release and β2-adrenoceptor desensitisation in human lung mast cells and airway smooth muscle cells.
Measured FcεRI-dependent histamine release using a radioenzymatic assay.
Assessed β2-adrenoceptor desensitisation by VASP phosphorylation in HMC-1 and ASM cells.
Conducted long-term incubations (24 hours) with β2-agonists to observe effects on desensitisation.
Both olodaterol and formoterol inhibited histamine release from lung mast cells with similar IC50 values.
Olodaterol induced VASP phosphorylation more effectively in HMC-1 cells compared to formoterol.
Long-term exposure led to β2-adrenoceptor desensitisation, with formoterol inducing significant desensitisation in ASM cells while olodaterol did not.

Abstract

Background: The novel ultra-long-acting β 2 -adrenoceptor agonist olodaterol has been developed for the management of asthma and COPD. Aims and Objectives: To compare the effects of olodaterol with formoterol and salbutamol on FcεRI-dependent human lung mast cell (HLMC) histamine release, and on β 2 -adrenoceptor (β 2 -AR) desensitisation in HLMCs, the HMC-1 human mast cell line and human airway smooth muscle (ASM) cells. Experimental Approach: FcεRI-dependent histamine release was measured using a radioenzymatic assay. β 2 -AR desensitisation was measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation (HMC-1 and ASM) and histamine release (HLMCs). Key Results: Olodaterol and formoterol inhibited FcεRI-dependent HLMC histamine release (IC 50 : 6.7 x 10 -11 M and 6.9 x 10 -11 M, respectively). Olodaterol was more potent than formoterol at inducing VASP phosphorylation in HMC-1 cells (EC 50 : 8.1 x 10 -11 M and 4.2 x 10 -10 M, respectively) (p<0.001). Olodaterol was more potent than formoterol at inducing VASP phosphorylation in ASM cells (EC 50 : 8.3 x 10 -10 M and 1.6 x 10 -8 M, respectively) (p<0.04). Long-term (24 h) incubation with all β 2 -agonists induced mast cell β 2 -AR desensitisation. At their EC 50 concentrations, formoterol induced ASM β 2 -AR desensitisation (p<0.001) but olodaterol did not (p<0.05 compared to formoterol). Conclusions and Implications: Olodaterol is a potent, effective inhibitor of FcεRI-dependent HLMC mediator release, with a less pronounced desensitisation in ASM cells compared to formoterol at moderate doses.

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