On October 23, 2020, PNAS published “The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR“.
Odorant sensing GPCRs are the largest gene family in the human genome. The team previously found multiple olfactory receptors and their obligate downstream effectors expressed in the smooth muscle of human bronchi. However, the extent to which odorant-sensing receptors (and the ligands to which they respond) on airway smooth muscle (ASM) are physiologically relevant is not established. Here the team shows that a monoterpene nerol activates the odorant receptor OR2W3 to relax ASM in both cell and tissue models. Surprisingly, the mechanism of action of OR2W3-mediated ASM relaxation involves paradoxical increases in [Ca2+]i that invoke a cooperative activation of TMEM16A and CFTR to compartmentalize calcium and regulate excitation-contraction coupling in human ASM cells.
Among the many contributors to this research are Reynold Paniettieri, Jr, M.D., Vice Chancellor for Translational Medicine and Science; Joseph Jude, Ph.D. Assistant Research Professor, Ernest Mario School of Pharmacy; Cynthia Kozoil-White, Ph.D. Assistant Professor, Robert Wood Johnson Medical School; and Steven S. An, Ph.D., Director of Bioengineering, RITMS.