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Olfactory receptors discovered in human bronchi.

Abnormalities in human airway smooth muscle cell function and structure play critical roles in chronic inflammatory airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. One key feature in these diseases is narrowing of the airway, which is caused by an increase in the mass of airway smooth muscles due to the hyperplasia and/or hypertrophy of the human airway smooth muscle cells.  Now, a study from researchers led by Ruhr-Universität Bochum identifies two types of olfactory receptors in the human muscle cells of bronchi. The team state that their findings suggest if these receptors are activated by binding an odorant, where the bronchi dilate and contract, they could be a potential approach for asthma therapy.  The study is published in the journal Frontiers in Physiology.

Previous studies show that olfactory receptors (ORs) represent the largest supergene family within the class of G protein-coupled receptors; they detect volatile odorant molecules by specific binding. Originally, olfactory sensory neurons in the nose were thought to exclusively express ORs. However, emerging data demonstrate that OR expression is not restricted to the nose and can be found in various human tissues. In the last decade, ORs were shown to regulate essential physiological functions, such as the regeneration of keratinocytes, sperm motility, and the inhibition of prostate cancer and hepatocarcinoma cell proliferation.  The current study shows that different ORs are expressed at the mRNA and protein levels in human airway smooth muscle cells.

The current study shows that the human ORs, OR1D2 and OR2AG1, are expressed at the RNA and protein levels in human airway smooth muscle cells.  Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca2+ increases in human airway smooth muscle cells via a cAMP-dependent signalling pathway.  Results show that the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of human airway smooth muscle cells, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility.  Data findings show that OR1D2 activation induced the secretion of IL-8 and GM-CSF.

Results show that amyl butyrate, a fruity scent with banana and apricot notes, stimulates the OR2AG1 receptor, and once the odorant binds, bronchioles relax and dilate. The lab state that this effect was so strong it could reverse the effect of histamine. They go on to note that histamine is the substance released by the body if a person suffers from allergic asthma, which leads to constriction of the bronchi.

The researchers state that amyl butyrate triggers the same signalling pathways in the muscle cells as in the olfactory cells in the nose.  They go on to add that the second receptor OR1D2 is sensitive to scents with floral, oily notes, for example lilial or bourgeonal. Data shows that when the odorant binds to the receptor, the effect is opposite to that of the OR2AG1 receptor, in that the bronchial muscles contract and pro-inflammatory substances are released from the cells.

The team surmise their findings provide the first evidence that ORs are functionally expressed in human airway smooth muscle cells and regulate pathophysiological processes. For the future, the researchers state that ORs might be new therapeutic targets for these diseases, and blocking ORs could be a new strategy for the treatment of early-stage chronic inflammatory lung diseases.

Source: Ruhr-Universität Bochum

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