Synthetic bastadins modify the activity of ryanodine receptors in cultured cerebellar granule cells

dc.contributor.author	Zieminska, E	en
dc.contributor.author	Stafiej, A	en
dc.contributor.author	Pitsinos, EN	en
dc.contributor.author	Couladouros, EA	en
dc.contributor.author	Moutsos, V	en
dc.contributor.author	Kozlowska, H	en
dc.contributor.author	Toczylowska, B	en
dc.contributor.author	Lazarewicz, JW	en
dc.date.accessioned	2014-06-06T06:47:28Z
dc.date.available	2014-06-06T06:47:28Z
dc.date.issued	2007	en
dc.identifier.issn	1424862X	en
dc.identifier.uri	http://dx.doi.org/10.1159/000107650	en
dc.identifier.uri	http://62.217.125.90/xmlui/handle/123456789/3608
dc.subject	Caffeine	en
dc.subject	Calcium mobilization	en
dc.subject	Neurons	en
dc.subject	Primary culture	en
dc.subject	Thapsigargin	en
dc.subject.other	bast217b	en
dc.subject.other	bast218f6	en
dc.subject.other	bast240	en
dc.subject.other	bast268	en
dc.subject.other	bastadin 10	en
dc.subject.other	bastadin 5	en
dc.subject.other	caffeine	en
dc.subject.other	diphenyl ether derivative	en
dc.subject.other	fluo 3	en
dc.subject.other	ryanodine receptor 2	en
dc.subject.other	tacrolimus	en
dc.subject.other	thapsigargin	en
dc.subject.other	unclassified drug	en
dc.subject.other	animal cell	en
dc.subject.other	article	en
dc.subject.other	brain nerve cell	en
dc.subject.other	calcium cell level	en
dc.subject.other	calcium transport	en
dc.subject.other	confocal microscopy	en
dc.subject.other	controlled study	en
dc.subject.other	granule cell	en
dc.subject.other	nonhuman	en
dc.subject.other	rat	en
dc.subject.other	synthesis	en
dc.subject.other	Animals	en
dc.subject.other	Caffeine	en
dc.subject.other	Calcium	en
dc.subject.other	Calcium Signaling	en
dc.subject.other	Cerebellum	en
dc.subject.other	Molecular Structure	en
dc.subject.other	Neurons	en
dc.subject.other	Phenyl Ethers	en
dc.subject.other	Porifera	en
dc.subject.other	Rats	en
dc.subject.other	Rats, Wistar	en
dc.subject.other	Ryanodine Receptor Calcium Release Channel	en
dc.subject.other	Tacrolimus	en
dc.subject.other	Tacrolimus Binding Proteins	en
dc.subject.other	Thapsigargin	en
dc.title	Synthetic bastadins modify the activity of ryanodine receptors in cultured cerebellar granule cells	en
heal.type	journalArticle	en
heal.identifier.primary	10.1159/000107650	en
heal.publicationDate	2007	en
heal.abstract	Although the interactions of several natural bastadins with the RyR1 isoform of the ryanodine receptor in sarcoplasmic reticulum has been described, their structure-dependent interference with the RyR2 isoform, mainly expressed in cardiac muscle and brain neurons, has not been studied. In this work, we examined calcium transients induced by natural bastadin 10 and several synthetic bastadins in cultured cerebellar granule cells known to contain RyR2. The fluorescent calcium indicator fluo-3 and confocal microscopy were used to evaluate changes in the intracellular Ca2+ concentration (Ca i), and the involvement of ryanodine receptors was assessed using pharmacological tools. Our results demonstrate that apart from the inactive BAST218F6 (a bisdebromo analogue of bastadin 10), synthetic bastadin 5, and synthetic analogues BAST217B, BAST240 and BAST268 (at concentrations >20 μM) increased Cai in a concentration-dependent, ryanodine- and FK-506-sensitive way, with a potency significantly exceeding that of 20 mM caffeine. Moreover, the same active bastadins at a concentration of 5 μM in the presence of ryanodine prevented a thapsigargin-induced increase in Ca i. These results indicate that bastadins, acting in a structure-dependent manner, modify the activity of RyR2 in primary neuronal culture and provide new information about structure-related pharmacological properties of bastadins. Copyright © 2007 S. Karger AG.	en
heal.journalName	NeuroSignals	en
dc.identifier.issue	6	en
dc.identifier.volume	15	en
dc.identifier.doi	10.1159/000107650	en
dc.identifier.spage	283	en
dc.identifier.epage	292	en