Journal club 2015.07.10.

HTR7 Mediates Serotonergic Acute and Chronic Itch

HTR7 Mediates Serotonergic Acute and Chronic Itch

Takeshi Morita,1,2,7 Shannan P. McClain,1,7 Lyn M. Batia,1 Maurizio Pellegrino,1 Sarah R. Wilson,1,2 Michael A. Kienzler,3 Kyle Lyman,3 Anne Sofie Braun Olsen,3 Justin F. Wong,1 Cheryl L. Stucky,4 Rachel B. Brem,5,6,* and Diana M. Bautista1,2,* 1Department of Molecular & Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720-3200, USA 2Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
3Neurobiology Course, Marine Biological Laboratory, Woods Hole, MA 02543, USA
4Departments of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA 5Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
6Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA
7Co-first author
*Correspondence: rbrem@buckinstitute.org (R.B.B.), dbautista@berkeley.edu (D.M.B.) http://dx.doi.org/10.1016/j.neuron.2015.05.044

SUMMARY
Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-re- gulated with itch behavior. This survey led to the discovery of the serotonin receptor HTR7 as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, in- cluding atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 dis- played reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.