title: Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs.
abstract: Several peptide fragments are produced by proteolytic cleavage of the opioid peptide precursor proenkephalin A, and among these are a number of enkephalin fragments, in particular bovine adrenal medulla peptide 22 (BAM22). These peptide products have been implicated in diverse biological functions, including analgesia. We have cloned a newly identified family of 'orphan' G protein--coupled receptors (GPCRs) and demonstrate that BAM22 and a number of its fragments bind to and activate these receptors with nanomolar affinities. This family of GPCRs is uniquely localized in the human and rat small sensory neuron, and we called this family the sensory neuron--specific G protein--coupled receptors (SNSRs). Receptors of the SNSR family are distinct from the traditional opioid receptors in their insensitivity to the classical opioid antagonist naloxone and poor activation by opioid ligands. The unique localization of SNSRs and their activation by proenkephalin A peptide fragments indicate a possible function for SNSRs in sensory neuron regulation and in the modulation of nociception.
authors.affiliation: AstraZeneca R&D Montreal, 7171 Frederick-Banting, Ville Saint-Laurent, Quebec H4S 1Z9, Canada. paola.lembo@astrazeneca.com
authors.forename: Paola M C
authors.initials: PM
authors.lastname: Lembo
authors.forename: Eric
authors.initials: E
authors.lastname: Grazzini
authors.forename: Thierry
authors.initials: T
authors.lastname: Groblewski
authors.forename: Dajan
authors.initials: D
authors.lastname: O'Donnell
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Roy
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Cyrla
authors.initials: C
authors.lastname: Hoffert
authors.forename: Jack
authors.initials: J
authors.lastname: Cao
authors.forename: Ralf
authors.initials: R
authors.lastname: Schmidt
authors.forename: Manon
authors.initials: M
authors.lastname: Pelletier
authors.forename: Maryse
authors.initials: M
authors.lastname: Labarre
authors.forename: Mylene
authors.initials: M
authors.lastname: Gosselin
authors.forename: Yves
authors.initials: Y
authors.lastname: Fortin
authors.forename: Denis
authors.initials: D
authors.lastname: Banville
authors.forename: S H
authors.initials: SH
authors.lastname: Shen
authors.forename: Peter
authors.initials: P
authors.lastname: Ström
authors.forename: Kemal
authors.initials: K
authors.lastname: Payza
authors.forename: Andy
authors.initials: A
authors.lastname: Dray
authors.forename: Philippe
authors.initials: P
authors.lastname: Walker
authors.forename: Sultan
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D004622:Embryo, Mammalian / Q000502:physiology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014018:Tissue Distribution
chemical_list: D004745:Enkephalins; D008024:Ligands; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011498:Protein Precursors; D011956:Receptors, Cell Surface; C029992:proenkephalin; D009270:Naloxone; D019204:GTP-Binding Proteins; D002118:Calcium