title: 4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator.
abstract: Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. Here, we provide identify 4-chlorophenylguanidine (4-CPG) as an ASIC3 positive allosteric modulator and newest member of the growing group of guanidine modulators of ASICs. Furthermore, the 4-CPG reversed the effects of ASIC3 desensitization. The molecule 4-CPG offers a novel chemical backbone for the design of new ASIC3 ligands to study ASIC3 in vivo.
authors.affiliation: Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Amruta S
authors.initials: AS
authors.lastname: Agharkar
authors.affiliation: Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: eric.b.gonzales@unthsc.edu.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Gonzales
mesh_terms: D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D019791:Guanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D062687:Sodium Channel Agonists / Q000494:pharmacology*
chemical_list: D062565:Acid Sensing Ion Channels; D062687:Sodium Channel Agonists; C478080:chlorophenylguanidine; D019791:Guanidine
keywords: Acid-sensing ion channel 3; Guanidine; Neuroscience