Next Article in Journal
For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors
Previous Article in Journal
Colletotrichum Gloesporioides Inhibition In Situ by Chitosan-Ruta graveolens Essential Oil Coatings: Effect on Microbiological, Physicochemical, and Organoleptic Properties of Guava (Psidium guajava L.) during Room Temperature Storage
Open AccessBrief Report

Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3)

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
2
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(9), 401; https://doi.org/10.3390/biom9090401
Received: 3 July 2019 / Revised: 16 August 2019 / Accepted: 19 August 2019 / Published: 22 August 2019
Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs—peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain. View Full-Text
Keywords: acid-sensing ion channel (ASIC); endogenous neuropeptide; electrophysiology; signaling; neuroscience; agonist of receptor acid-sensing ion channel (ASIC); endogenous neuropeptide; electrophysiology; signaling; neuroscience; agonist of receptor
Show Figures

Figure 1

MDPI and ACS Style

Osmakov, D.I.; Koshelev, S.G.; Ivanov, I.A.; Andreev, Y.A.; Kozlov, S.A. Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3). Biomolecules 2019, 9, 401.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop