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Alkaloid Lindoldhamine Inhibits Acid-Sensing Ion Channel 1a and Reveals Anti-Inflammatory Properties
- Source :
- Toxins, Volume 11, Issue 9, Toxins, Vol 11, Iss 9, p 542 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- 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&rsquo<br />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&rsquo<br />s response to physiologically-relevant stimuli of pH 6.5&ndash<br />6.85 with IC50 range 150&ndash<br />9 &mu<br />M, 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&rsquo<br />s adjuvant-induced thermal hyperalgesia and inflammation<br />however, this administration did not affect the pain response to an intraperitoneal injection of acetic acid (which correlated well with the function of ASIC1a in the peripheral nervous system). Thus, we describe lindoldhamine as a novel antagonist of the ASIC1a channel that could provide new approaches to drug design and structural studies regarding the determinants of ASIC1a activation.
- Subjects :
- Male
Hot Temperature
medicine.drug_class
lindoldhamine
Health, Toxicology and Mutagenesis
medicine.medical_treatment
Intraperitoneal injection
Freund's Adjuvant
Anti-Inflammatory Agents
lcsh:Medicine
Pain
Pharmacology
Toxicology
acid-sensing ion channel subtype 1a
bisbenzylisoquinoline alkaloid
Anti-inflammatory
Article
03 medical and health sciences
Mice
Xenopus laevis
0302 clinical medicine
medicine
Benzene Derivatives
Animals
nociception
Acid-sensing ion channel
Ion channel
030304 developmental biology
Acetic Acid
Inflammation
0303 health sciences
Chemistry
Alkaloid
lcsh:R
Antagonist
Acid Sensing Ion Channels
Electrophysiology
medicine.anatomical_structure
Acid Sensing Ion Channel Blockers
Hyperalgesia
Peripheral nervous system
Oocytes
Quinolines
Female
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20726651
- Volume :
- 11
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Toxins
- Accession number :
- edsair.doi.dedup.....bf9a8fecc65b3c39874f11a6ee817a52