Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i>
Excessive release of glutamate induces excitotoxicity and causes neuronal damage in several neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for preventing and treating neurological disorders. Dehydrocorydaline (DHC), an active alkaloid compound isolated...
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/3/960 |
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| author | Tzu-Yu Lin I-Yen Chen Ming-Yi Lee Cheng-Wei Lu Kuan-Ming Chiu Su-Jane Wang |
| author_facet | Tzu-Yu Lin I-Yen Chen Ming-Yi Lee Cheng-Wei Lu Kuan-Ming Chiu Su-Jane Wang |
| author_sort | Tzu-Yu Lin |
| collection | DOAJ |
| description | Excessive release of glutamate induces excitotoxicity and causes neuronal damage in several neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for preventing and treating neurological disorders. Dehydrocorydaline (DHC), an active alkaloid compound isolated from <i>Corydalis yanhusuo</i>, possesses neuroprotective capacity. The present study investigated the effect of DHC on glutamate release using a rat brain cortical synaptosome model. Our results indicate that DHC inhibited 4-aminopyridine (4-AP)-evoked glutamate release and elevated intrasynaptosomal calcium levels. The inhibitory effect of DHC on 4-AP-evoked glutamate release was prevented in the presence of the vesicular transporter inhibitor bafilomycin A1 and the N- and P/Q-type Ca<sup>2+</sup> channel blocker ω-conotoxin MVIIC but not the intracellular inhibitor of Ca<sup>2+</sup> release dantrolene or the mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibitor CGP37157. Moreover, the inhibitory effect of DHC on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) inhibitor PD98059. Western blotting data in synaptosomes also showed that DHC significantly decreased the level of ERK1/2 phosphorylation and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. Together, these results suggest that DHC inhibits presynaptic glutamate release from cerebrocortical synaptosomes by suppressing presynaptic voltage-dependent Ca<sup>2+</sup> entry and the MAPK/ERK/synapsin I signaling pathway. |
| first_indexed | 2024-03-09T23:27:37Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:27:37Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b98dd72d067b42568838e04253f680c22023-11-23T17:15:18ZengMDPI AGMolecules1420-30492022-01-0127396010.3390/molecules27030960Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i>Tzu-Yu Lin0I-Yen Chen1Ming-Yi Lee2Cheng-Wei Lu3Kuan-Ming Chiu4Su-Jane Wang5Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, TaiwanDepartment of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, TaiwanDivision of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei 22060, TaiwanDepartment of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, TaiwanDivision of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei 22060, TaiwanSchool of Medicine, Fu Jen Catholic University, New Taipei City 24205, TaiwanExcessive release of glutamate induces excitotoxicity and causes neuronal damage in several neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for preventing and treating neurological disorders. Dehydrocorydaline (DHC), an active alkaloid compound isolated from <i>Corydalis yanhusuo</i>, possesses neuroprotective capacity. The present study investigated the effect of DHC on glutamate release using a rat brain cortical synaptosome model. Our results indicate that DHC inhibited 4-aminopyridine (4-AP)-evoked glutamate release and elevated intrasynaptosomal calcium levels. The inhibitory effect of DHC on 4-AP-evoked glutamate release was prevented in the presence of the vesicular transporter inhibitor bafilomycin A1 and the N- and P/Q-type Ca<sup>2+</sup> channel blocker ω-conotoxin MVIIC but not the intracellular inhibitor of Ca<sup>2+</sup> release dantrolene or the mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibitor CGP37157. Moreover, the inhibitory effect of DHC on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) inhibitor PD98059. Western blotting data in synaptosomes also showed that DHC significantly decreased the level of ERK1/2 phosphorylation and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. Together, these results suggest that DHC inhibits presynaptic glutamate release from cerebrocortical synaptosomes by suppressing presynaptic voltage-dependent Ca<sup>2+</sup> entry and the MAPK/ERK/synapsin I signaling pathway.https://www.mdpi.com/1420-3049/27/3/960dehydrocorydalineglutamate releaseCa<sup>2+</sup> influxsynaptosomesneuroprotectionMAPK/ERK/synapsin I |
| spellingShingle | Tzu-Yu Lin I-Yen Chen Ming-Yi Lee Cheng-Wei Lu Kuan-Ming Chiu Su-Jane Wang Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> Molecules dehydrocorydaline glutamate release Ca<sup>2+</sup> influx synaptosomes neuroprotection MAPK/ERK/synapsin I |
| title | Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> |
| title_full | Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> |
| title_fullStr | Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> |
| title_full_unstemmed | Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> |
| title_short | Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from <i>Corydalis yanhusuo</i> |
| title_sort | inhibition of glutamate release from rat cortical nerve terminals by dehydrocorydaline an alkaloid from i corydalis yanhusuo i |
| topic | dehydrocorydaline glutamate release Ca<sup>2+</sup> influx synaptosomes neuroprotection MAPK/ERK/synapsin I |
| url | https://www.mdpi.com/1420-3049/27/3/960 |
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