Back to Search
Start Over
Neferine, a bisbenzylisoquinoline alkaloid of Nelumbo nucifera, inhibits glutamate release in rat cerebrocortical nerve terminals through 5-HT 1A receptors.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2020 Dec 15; Vol. 889, pp. 173589. Date of Electronic Publication: 2020 Sep 19. - Publication Year :
- 2020
-
Abstract
- Neferine, a bisbenzylisoquinoline alkaloid present in Nelumbo nucifera, has been reported to exhibit neuroprotective effects. Because reduced glutamatergic transmission through inhibition of glutamate release has been proposed as a mechanism of neuroprotection, we investigated whether and how neferine inhibits glutamate release in the nerve terminals of the cerebral cortex of rats. The results demonstrated that neferine inhibits the glutamate release that is evoked by the potassium channel blocker 4-aminopyridine, doing so in a dose-dependent manner. This effect was prevented by removing extracellular calcium and blocking vesicular transporters or N- and P/Q-type calcium channels but not by blocking glutamate transporters. Neferine decreased the 4-aminopyridine-stimulated elevation in intrasynaptosomal calcium concentration; however, it had no effect on the synaptosomal membrane potential. The inhibition of glutamate release by neferine was also eliminated by the selective 5-hydroxytryptamine 1A (5HT <subscript>1A</subscript> ) receptor antagonist WAY100635, Gi/o protein inhibitor pertussis toxin, adenylyl cyclase inhibitor MDL12330A, and protein kinase A inhibitor H89. Moreover, immunocytochemical analysis revealed the presence of 5-HT <subscript>1A</subscript> receptor proteins in the vesicular transporter of glutamate type 1 positive synaptosomes. The molecular docking study also demonstrated that neferine exhibited the highest binding affinity with 5-HT <subscript>1A</subscript> receptors (Autodock scores for 5-HA <subscript>1A</subscript>  = -11.4 kcal/mol). Collectively, these results suggested that neferine activates 5-HT <subscript>1A</subscript> receptors in cortical synaptosomes, which decreases calcium influx and glutamate release through the activation of Gi/o protein and the inhibition of adenylyl cyclase/cAMP/protein kinase A cascade.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Alkaloids isolation & purification
Alkaloids pharmacology
Animals
Benzylisoquinolines chemistry
Benzylisoquinolines isolation & purification
Cerebral Cortex drug effects
Dose-Response Relationship, Drug
Drugs, Chinese Herbal isolation & purification
Drugs, Chinese Herbal pharmacology
Excitatory Amino Acid Antagonists chemistry
Excitatory Amino Acid Antagonists isolation & purification
Excitatory Amino Acid Antagonists pharmacology
Male
Molecular Docking Simulation
Nerve Endings drug effects
Protein Structure, Secondary
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A chemistry
Benzylisoquinolines pharmacology
Cerebral Cortex metabolism
Glutamic Acid metabolism
Nelumbo
Nerve Endings metabolism
Receptor, Serotonin, 5-HT1A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 889
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32961171
- Full Text :
- https://doi.org/10.1016/j.ejphar.2020.173589