Ectopic olfactory receptors in the respiratory system

Abstract

New findings and concepts on a role of so-called “ectopic” chemosensory receptors arise recently. The ectopic receptors are expressed outside their classical localization (nasal cavity) and referred to as extra-nasal olfactory receptors. Functional investigations of the ectopic olfactory receptors in the lungs are also ongoing. To date, it is well-known that molecules of odorous substances (odorants) bind to the G-protein-associated olfactory receptor (Gαolf) that can activate type III adenylate cyclase and increase concentration of a secondary messenger, cyclic adenosine monophosphate (cAMP). In turn, this induces the opening of cAMP-dependent cationic channels including calcium channels. Olfactory receptor activation in neuroendocrine cells of the lungs affected serotonin release which decreased after the stimulation of those cells by an odorant. Amyl butyrate and burgenal, agonists of OR2AG1 and OR1D2 olfactory receptors, respectively, affect smooth muscle contractibility in human bronchi. Amyl butyrate inhibits histamine-induces muscle contractibility, whereas burgenal increases the smooth muscle contractibility. Both the processes are mediated by cAMP-dependent increase in the intracellular calcium concentration. Data have been published about the receptor expression on immune cells such as monocytes, natural killers, T- and B-lymphocites, and polymorphonuclears. Ectopic olfactory receptors are thought to participate in modulation (controlling) of intrinsic cell functions which provide a special role of inflammatory cells in asthma. In future, the olfactory receptor modulation could be probably used as a novel therapeutic approach in asthma and other chronic inflammatory lung diseases.