Melatonin MT < sub > 2 < /sub > receptor is expressed and potentiates contraction in human airway smooth muscle

Am J Physiol Lung Cell Mol Physiol. 2021 Oct 6. doi: 10.1152/ajplung.00273.2021. Online ahead of print.ABSTRACTNocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor which couples to both Gq and Gi proteins, and the MT2 receptor which couples to Gi. We investigated whether melatonin receptors are expressed on airway smooth muscle, whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i) which modulate airway smooth muscle tone, and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10 - 100 µM) or the non-selective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gαi protein inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin si...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research