|
KMID : 1161420210240030209
|
|
Journal of Medicinal Food
2021 Volume.24 No. 3 p.209 ~ p.217
|
|
|
Albanin A, Derived from the Root Bark of Morus alba L., Depresses Glutamate Release in the Rat Cerebrocortical Nerve Terminals via Ca2+/Calmodulin/Adenylate Cyclase 1 Suppression
|
|
Chang Yi
Hung Chi Feng
Ko Horng Huey
Wang Su Jane
|
|
|
Abstract
|
|
|
|
Decreasing synaptic release of glutamate may counteract glutamate excitotoxicity in many neurological diseases. In this study, we investigated the effect of albanin A, a constituent in the root bark of Morus alba L., on the release of glutamate in rat cerebral cortex nerve endings (synaptosomes). We found that albanin A at 5?30μM suppressed 4-aminopyridine (4-AP)-induced release of glutamate. This phenomenon was abolished by extracellular calcium removal or by vesicular transporter inhibition, and was associated with a decrease in intrasynaptosomal Ca2+ levels. However, albanin A had no effect on the synaptosomal membrane potential. The inhibition of N- and P/Q-type Ca2+ channels, calmodulin, adenylate cyclase (AC), and protein kinase A, abolished the effect of albanin A on the glutamate release evoked by 4-AP. Moreover, the albanin A-mediated inhibition of glutamate release was prevented by the Ca2+/calmodulin-stimulated AC1 inhibitor. Western blot showed that AC1, but not AC8, was presented in the synaptosomes, and albanin A reduced 4-AP-induced increases in synaptosomal cyclic adenosine monophosphate content. In addition, albanin A pretreatment substantially attenuated neuronal damage in a rat model of kainic acid-induced glutamate excitotoxicity. Our data reveal that albanin A suppresses glutamate release by decreasing Ca2+/calmodulin/AC1 activation in synaptosomes and exerts neuroprotective effect in vivo.
|
|
|
KEYWORD
|
|
|
AC1, albanin A, Ca2+/calmodulin, glutamate excitotoxicity, kainic acid, presynaptic glutamate release
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|