Journal
SYNAPSE
Volume 62, Issue 12, Pages 890-901Publisher
WILEY
DOI: 10.1002/syn.20568
Keywords
honokiol; glutamate release; voltage-dependent Ca2+ influx; protein kinase C; synaptosomes; cerebral cortex
Categories
Funding
- National Science Council of Taiwan, Republic of China [NSC 96-2628-B-030-001-MY3]
- Changhua Christian Hospital [CCH-FJU-96-14]
Ask authors/readers for more resources
The effect of honokiol, an active component of Magnolia officinalis, on glutamate release from isolated nerve terminals (synaptosomes) was examined. Honokiol potently inhibited 4-aminopyridine (4-AP)-evoked glutamate release in a concentration-dependent manner, and this effect resulted from a reduction of vesicular exocytosis and not from an inhibition of Ca2+-independent efflux via glutamate transporter. The inhibitory action of honokiol was not due to decreasing synaptosomal excitability or directly interfering with the release process at some point subsequent to Ca2+ influx, because honokiol did not alter the 4-AP-evoked depolarization of the synaptosomal plasma membrane potential or Ca2+ ionophore ionomycin-induced glutamate release. Rather, examination of the effect of honokiol on cytosolic [Ca2+] revealed that the diminution of glutamate release could be attributed to a reduction ill voltage-dependent Ca2+ influx. Consistent with this, the honokiol-mediated inhibition of 4-AP-evoked glutamate release was completely prevented in synaptosomes pretreated with a wide-spectrum blocker of N-, P-, and Q-type Ca2+ channels, omega-conotoxin MVIIC. In addition, honokiol modulation of 4-AP-evoked glutamate release appeared to involve a protein kinase C (PKC) signaling cascade, in so far as pretreatment of synaptosomes with the PKC inhibitors Ro318220 or GF109203X all effectively occluded the inhibitory effect of honokiol. Furthermore, honokiol attenuated 4-AP-induced phosphorylation of PKC. Together, these results suggest that bonokiol effects a decrease in PKC activation, which subsequently attenuates the Ca2+ entry through voltage-dependent N- and P/Q-type Ca2+ channels to cause a decrease in evoked glutamate exocytosis. These actions of honokiol may contribute to its neuroprotective effect in excitotoxic injury. Synapse 62:890-901, 2008. (C) 2008 Wiley-Liss. Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available