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Excerpt
Nociceptive sensory neurons are key players in both acute and chronic pain and their somata are located in dorsal root ganglia (DRG). They have been the focus of intense research to identify molecular targets for pain neurotransmission. Among these, a large number of “orphan” G protein-coupled receptors (GPCRs) specifically expressed in the somatosensory system have been investigated. In this study, a newly identified family of GPCRs is cloned and found to be uniquely localized in human and rat DRGs. Using an assay based on intracellular calcium mobilization, these sensory neuron-specific G protein-coupled receptors (SNSRs) are shown to display a different pharmacology as compared to the opioid-receptor family. Interestingly, they are selectively activated at nanomolar concentrations by the opioid bovine adrenal medulla peptide 22 (BAM22), one of the fragments produced by proteolytic cleavage of the opioid precursor proenkephalin A. The analysis of a shorter version of BAM22 demonstrates that amino acids 8-22 are necessary for SNSRs activation, whereas the opioid part of peptide is not required, suggesting a complete dissociation between opioid and SNSR agonist activities in BAM22.
At present, the physiological role of the BAM22/SNSRs system is unknown. The expression pattern of SNSRs, restricted to DRG neurons, indicates a possible role for this novel receptor family in sensory neuron regulation and in the modulation of nociception. Moreover, the cloning of SNSR presented in this study may lead to new pain modulatory peptides and ligands, potentially useful for treatment of opiates-resistant pain conditions.
