Alkaloid lindoldhamine inhibits acid-sensing ion channel 1a and reveals anti-inflammatory properties
Osmakov D. I., Koshelev S. G., Palikov V. A., Palikova Y. A., Shaykhutdinova E. R., Dyachenko I. A., Andreev Ya. A., Kozlov S. A.
Toxins
Vol.11, Issue9, Num.542
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.3390/toxins11090542
Аннотация:
Acid-sensing ion channels (ASICs), which are present in almost all types of neurons, play an important role in physiological and pathological processes. The ASIC1a subtype is the most sensitive channel to the medium's acidification, and it plays an important role in the excitation of neurons in the central nervous system. Ligands of the ASIC1a channel are of great interest, both fundamentally and pharmaceutically. Using a two-electrode voltage-clamp electrophysiological approach, we characterized lindoldhamine (a bisbenzylisoquinoline alkaloid extracted from the leaves of Laurus nobilis L.) as a novel inhibitor of the ASIC1a channel. Lindoldhamine significantly inhibited the ASIC1a channel's response to physiologically-relevant stimuli of pH 6.5-6.85 with IC50 range 150-9 μM, but produced only partial inhibition of that response to more acidic stimuli. In mice, the intravenous administration of lindoldhamine at a dose of 1 mg/kg significantly reversed complete Freund's adjuvant-induced
Ключевые слова:
Acid-sensing ion channel subtype 1a; Bisbenzylisoquinoline alkaloid; Inflammation; Lindoldhamine; Nociception
acetic acid; acid sensing ion channel; acid sensing ion channel 1a; alkaloid; Freund adjuvant; lindoldhamine; unclassified drug; abdominal constriction test; acidification; animal cell; animal experiment; animal model; antiinflammatory activity; Article; chemical structure; controlled study; dose response; drug design; drug efficacy; electrophysiological procedures; Freund adjuvant-induced inflammation; IC50; in vivo study; Laurus nobilis; long duration stimulus test; male; mouse; nerve cell stimulation; nervous system electrophysiology; nonhuman; number of writhes; oocyte retrieval; peripheral nervous system; thermal hyperalgesia; thermal stimulation; visceral pain; voltage clamp technique; writhing test; Xenopus laevis
Язык текста: Английский
ISSN: 2072-6651
Osmakov D. I. Dmitrij Igorevich 1987-
Koshelev S. G.
Palikov V. A.
Palikova Y. A.
Shaykhutdinova E. R.
Dyachenko I. A.
Andreev Ya. A. Yaroslav Alekseevich 1979-
Kozlov S. A.
Осмаков Д. И. Дмитрий Игоревич 1987-
Кошелев С. Г.
Паликов В. А.
Паликова Y. А.
Шайхутдинова Е. Р.
Дяченко И. А.
Андреев Я. А. Ярослав Алексеевич 1979-
Козлов С. А.
Alkaloid lindoldhamine inhibits acid-sensing ion channel 1a and reveals anti-inflammatory properties
Текст визуальный непосредственный
Toxins
Vol.11, Issue9 Num.542
2019
Статья
Acid-sensing ion channel subtype 1a Bisbenzylisoquinoline alkaloid Inflammation Lindoldhamine Nociception
acetic acid acid sensing ion channel acid sensing ion channel 1a alkaloid Freund adjuvant lindoldhamine unclassified drug abdominal constriction test acidification animal cell animal experiment animal model antiinflammatory activity Article chemical structure controlled study dose response drug design drug efficacy electrophysiological procedures Freund adjuvant-induced inflammation IC50 in vivo study Laurus nobilis long duration stimulus test male mouse nerve cell stimulation nervous system electrophysiology nonhuman number of writhes oocyte retrieval peripheral nervous system thermal hyperalgesia thermal stimulation visceral pain voltage clamp technique writhing test Xenopus laevis
Acid-sensing ion channels (ASICs), which are present in almost all types of neurons, play an important role in physiological and pathological processes. The ASIC1a subtype is the most sensitive channel to the medium's acidification, and it plays an important role in the excitation of neurons in the central nervous system. Ligands of the ASIC1a channel are of great interest, both fundamentally and pharmaceutically. Using a two-electrode voltage-clamp electrophysiological approach, we characterized lindoldhamine (a bisbenzylisoquinoline alkaloid extracted from the leaves of Laurus nobilis L.) as a novel inhibitor of the ASIC1a channel. Lindoldhamine significantly inhibited the ASIC1a channel's response to physiologically-relevant stimuli of pH 6.5-6.85 with IC50 range 150-9 μM, but produced only partial inhibition of that response to more acidic stimuli. In mice, the intravenous administration of lindoldhamine at a dose of 1 mg/kg significantly reversed complete Freund's adjuvant-induced