Endogenous neuropeptide nocistatin is a direct agonist of acid-sensing ion channels (ASIC1, ASIC2 and ASIC3)
Osmakov D. I., Koshelev S. G., Ivanov I. A., Andreev Ya. A., Kozlov S. A.
Biomolecules
Vol.9, Issue9, Num.401
Опубликовано: 2019
Тип ресурса: Статья
Аннотация:
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 mec
Ключевые слова:
Acid-sensing ion channel (asic); Agonist of receptor; Electrophysiology; Endogenous neuropeptide; Neuroscience; Signaling
acid sensing ion channel; acid sensing ion channel 1; acid sensing ion channel 2; acid sensing ion channel 3; acid sensing ion channel blocking agent; gentamicin; mambalgin 2; nociceptin; nocistatin; unclassified drug; acid sensing ion channel; Asic1 protein, rat; Asic2 protein, rat; ASIC3 protein, rat; neuropeptide; nocistatin; opiate peptide; sodium channel stimulating agent; Article; controlled study; desensitization; drug synthesis; EC50; electrophysiology; electrospray mass spectrometry; flow rate; IC50; nerve cell; neutrophil; nonhuman; oocyte; reversed phase high performance liquid chromatography; Xenopus laevis; amino acid sequence; animal; chemistry; metabolism; rat; Acid Sensing Ion Channels; Amino Acid Sequence; Animals; Neuropeptides; Opioid Peptides; Rats; Sodium Channel Agonists
Язык текста: Английский
ISSN: 2218-273X
Osmakov D. I. Dmitrij Igorevich 1987-
Koshelev S. G.
Ivanov I. A.
Andreev Ya. A. Yaroslav Alekseevich 1979-
Kozlov S. A.
Осмаков Д. И. Дмитрий Игоревич 1987-
Кошелев С. Г.
Иванов И. А.
Андреев Я. А. Ярослав Алексеевич 1979-
Козлов С. А.
Endogenous neuropeptide nocistatin is a direct agonist of acid-sensing ion channels (ASIC1, ASIC2 and ASIC3)
Текст визуальный непосредственный
Biomolecules
Vol.9, Issue9 Num.401
2019
Статья
Acid-sensing ion channel (asic) Agonist of receptor Electrophysiology Endogenous neuropeptide Neuroscience Signaling
acid sensing ion channel acid sensing ion channel 1 acid sensing ion channel 2 acid sensing ion channel 3 acid sensing ion channel blocking agent gentamicin mambalgin 2 nociceptin nocistatin unclassified drug acid sensing ion channel Asic1 protein, rat Asic2 protein, rat ASIC3 protein, rat neuropeptide nocistatin opiate peptide sodium channel stimulating agent Article controlled study desensitization drug synthesis EC50 electrophysiology electrospray mass spectrometry flow rate IC50 nerve cell neutrophil nonhuman oocyte reversed phase high performance liquid chromatography Xenopus laevis amino acid sequence animal chemistry metabolism rat Acid Sensing Ion Channels Amino Acid Sequence Animals Neuropeptides Opioid Peptides Rats Sodium Channel Agonists
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 mec