Gangliosides and sialylcholesterol as modulators of synaptic functions.
Gangliosides were shown to enhance the release of acetylcholine from synaptosomes on stimulation. The influx of calcium ion into synaptosomes on membrane depolarization was increased by gangliosides. This was hypothesized to be an underlying mechanisms for the enhancement of acetylcholine release. Studies using calcium channel blockers revealed that four distinct types of voltage-dependent calcium channels occurred in cerebrocortical synapses, and that the N-type was primarily responsible for the evoked release of acetylcholine. An additional result suggests that gangliosides may act mainly on the N-type calcium channel. Cholinergic-specific gangliosides, Chol-1 alpha, were assumed to participate in the mechanism of high-affinity choline uptake. These two different actions of gangliosides were found to be mimicked by synthetic ganglioside analogs. Calcium influx was increased by alpha-sialylcholesterol, and choline uptake was accelerated by beta-sialylcholesterol. Gangliosides and sialylcholesterol having these apparently beneficial effects were shown to ameliorate decreased functions of synapses from aged brains.
Department of Membrane Biochemistry, Tokyo Metropolitan Institute of Gerontology, Japan. andos@tmig.or.jp
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Ando
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Tanaka
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Waki
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Kon
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Iwamoto
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Fukui
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology*; D002788:Cholesterol Esters / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002352:Carrier Proteins; D002788:Cholesterol Esters; D005732:Gangliosides; D026901:Membrane Transport Proteins; D012794:Sialic Acids; C065637:choline transporter; C055195:N-acetylneuraminyl cholesterol; D005677:G(M1) Ganglioside; C039129:GQ1b ganglioside; D002794:Choline; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium