title: Targeting ASIC3 for pain, anxiety, and insulin resistance.
abstract: The acid-sensing ion channel 3 (ASIC3) is a pH sensor that responds to mild extracellular acidification and is predominantly expressed in nociceptors. There is much interest in targeting ASIC3 to relieve pain associated with tissue acidosis, and selective drugs targeting ASIC3 have been used to relieve acid-evoked pain in animal models and human studies. There is accumulating evidence that ASIC3 is widely expressed in many neuronal and non-neuronal cells, such as neurons in the brain and adipose cells, albeit to a lesser extent than in nociceptors. Asic3-knockout mice have reduced anxiety levels and enhanced insulin sensitivity, suggesting that antagonizing ASIC3 has additional benefits. This view is tempered by recent studies suggesting that Asic3-knockout mice may experience cardiovascular disturbances. Due to the development of ASIC3 antagonists as analgesics, we review here the additional benefits, safety, risks, and strategy associated with antagonizing ASIC3 function.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Wu
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Sun
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Wong
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: C112231:ASIC3 protein, human; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels