The murine genome contains more than 50 Mas-related genes (Mrgs), subdivided into subfamilies termed MrgA, MrgB, MrgC, and MrgD, which encode orphan G protein-coupled receptors that are expressed by specific subsets of nociceptive afferent neurons (6-9). This diversity of Mrgs appears to be an atypical feature of mice (8), since rats and gerbils have
Table 3 Three Classes of Drug Targets on Sensory Neurons and Their Transmission Relays
Receptors and sensors on afferent nerve terminals 5-Hydroxytryptamine (5-HT3 and 5-HT4) receptors Adenosine A! and A2 receptors lonotropic purinoceptors of type P2X2, P2X3, and P2X2/3 Transient receptor potential ion channels of type TRPV1 and TRPV4 Acid-sensing ion channels of type ASIC1, ASIC2, ASIC3, and ASIC2b/3 Bradykinin B1 and B2 receptors Prostaglandin EP1; EP2, EP3, EP4 and IP receptors Protease-activated receptors of type PAR-1 and PAR-2 Cholecystokinin CCK1 receptors Corticotropin-releasing factor receptors Somatostatin sst2 receptors Ionotropic and metabotropic glutamate receptors m-, k- , and S-opioid receptors Cannabinoid CB1 receptors Orphan G protein-coupled receptors (Mrgs) Neurotrophin receptors Mechanosensitive K+ and Ca2+ channels Ion channels relevant to sensory neuron excitability and conduction Voltage-gated Ca2+ channels Voltage-gated K+ channels Tetrodotoxin-resistant voltage-gated Na+ channels Receptors for transmitters relevant to sensory neuron signaling Ionotropic and metabotropic glutamate receptors Calcitonin gene-related peptide receptors Tachykinin NK1, NK2, and NK3 receptors ^-Adrenoceptors m-, k- , and S-opioid receptors Cannabinoid CB1 receptors
Abbreviation: TRPV, transient receptor potential ion channels of the vanilloid type.
considerably fewer Mrg genes, and humans contain a related but nonorthologous family of genes, called MrgXs or SNSR. MrgD encodes an orphan G protein-coupled receptor termed TGR7, which is predominantly expressed in dorsal root ganglia (DRG) of rats and monkeys in which it is found on small diameter neurons bearing P2X3 purinoceptors and transient receptor potential ion channels of vanilloid type 1 (TRPV1) (9). It awaits to be elucidated which stimuli and agonists other than RF-amide-related peptides (6), proenkephalin A gene products (7), and p-alanine (9) can activate these receptors and whether Mrgs are relevant to visceral hypersensitivity.
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