A Diverse Family of GPCRs Expressed in Specific Subsets of Nociceptive Sensory Neurons
In vertebrates, peripheral chemosensory neurons express large families of G protein-coupled receptors (GPCRs), reflecting the diversity and specificity of stimuli they detect. However, somatosensory neurons, which respond to chemical, thermal, or mechanical stimuli, are more broadly tuned. Here we describe a family of approximately 50 GPCRs related to Mas1, called mrgs, a subset of which is expressed in specific subpopulations of sensory neurons that detect painful stimuli. The expression patterns of mrgs thus reveal an unexpected degree of molecular diversity among nociceptive neurons. Some of these receptors can be specifically activated in heterologous cells by RFamide neuropeptides such as NPFF and NPAF, which are analgesic in vivo. Thus, mrgs may regulate nociceptor function and/or development, including the sensation or modulation of pain.
Additional Information© 2001 Cell Press. Under an Elsevier user license. Received April 18, 2001; revised July 30, 2001. We thank David Mathog for help with computer analysis, Emma Dormand for help with confocal microscopy, Henry Lester for gracious assistance with Fura-2 imaging, Aurora Biosciences, Inc. for providing HEK-Gα15 cells, Gaby Mosconi for lab management, Jeongkyo Yoon for providing EGFP constructs, and Richard Axel and Kai Zinn for helpful discussions. Some of the sequence data reported in this paper were generated through the use of the Celera Discovery System and Celera Genomic's associated database. X.D. is a postdoctoral fellow of the American Cancer Society, and M.J.Z. is supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship, DRG-1581. D.J.A. is an Investigator of the Howard Hughes Medical Institute. S.H. and M.I.S. are supported by NIGMS grant no. GM-34236.
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