4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator

Amruta S Agharkar; Eric B Gonzales

doi:10.1016/j.jphs.2017.02.007

4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator

J Pharmacol Sci. 2017 Mar;133(3):184-186. doi: 10.1016/j.jphs.2017.02.007. Epub 2017 Feb 17.

Authors

Amruta S Agharkar¹, Eric B Gonzales²

Affiliations

¹ Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA.
² 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.

PMID: 28259560
DOI: 10.1016/j.jphs.2017.02.007

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.

Keywords: Acid-sensing ion channel 3; Guanidine; Neuroscience.

MeSH terms

Acid Sensing Ion Channels / physiology*
Animals
CHO Cells
Cricetulus
Guanidine / analogs & derivatives*
Guanidine / pharmacology
Hydrogen-Ion Concentration
Sodium Channel Agonists / pharmacology*

Substances

Acid Sensing Ion Channels
Sodium Channel Agonists
chlorophenylguanidine
Guanidine