Editors' ChoiceCalcium signaling

Calcilytics may help asthmatics breathe easier

Sci. Signal.  28 Apr 2015:
Vol. 8, Issue 374, pp. ec112
DOI: 10.1126/scisignal.aab4167

Calcium helps build strong bones. However, Yarova et al. show that extracellular calcium may contribute to inflammation and airway hyperresponsiveness in allergic asthma. Increased extracellular calcium activated airway smooth muscle cells through the calcium-sensing receptor (CaSR). Compared with healthy individuals, asthmatic patients, as well as a mouse model of allergic asthma, had higher amounts of CaSR in their airways. Indeed, extracellular calcium and other asthma-associated activators of CaSR increased airway hyperreactivity. Moreover, calcilytics—CaSR antagonists—prevented calcium-induced airway hyperreactivity in vitro and in vivo, supporting clinical testing of these drugs for asthmatics.

P. L. Yarova, A. L. Stewart, V. Sathish, R. D. Britt Jr., M. A. Thompson, A. P. P. Lowe, M. Freeman, B. Aravamudan, H. Kita, S. C. Brennan, M. Schepelmann, T. Davies, S. Yung, Z. Cholisoh, E. J. Kidd, W. R. Ford, K. J. Broadley, K. Rietdorf, W. Chang, M. E. Bin Khayat, D. T. Ward, C. J. Corrigan, J. P. T. Ward, P. J. Kemp, C. M. Pabelick, Y. S. Prakash, D. Riccardi, Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Sci. Transl. Med. 7, 284ra60 (2015). [Abstract]