Linked Life Data

15932592

Source:http://linkedlifedata.com/resource/pubmed/id/15932592

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-6-3
pubmed:abstractText
Neuroactive steroids can modulate brain excitability by interaction with several neurotransmitter receptor-associated channels. These compounds may thus exert profound influences on excitotoxic injury, i.e. neuronal cell death triggered by over-activation of glutamate receptors. It has been reported that pregnenolone sulphate (PS) and pregnenolone hemisuccinate (PHS) augment N-methyl-D-aspartate (NMDA) neurotoxicity in rat cultured neurons. Here we show that the effects of neuroactive steroids on AMPA cytotoxicity display features distinct from those on NMDA cytotoxicity. Concomitant application of PS (30-300 microm) attenuated, rather than augmented, AMPA neurotoxicity in cortical slice cultures in a concentration-dependent manner, whereas various other steroids including pregnenolone and PHS had no effect. Inhibition of steroid sulphatase by estrone-3-O-sulphamate led to a shift of the minimum effective concentration of PS against AMPA cytotoxicity from 30 to 10 microm. The protective action of PS was not affected by inhibition of protein synthesis or by blockade of glucocorticoid receptors, GABAA receptors or sigma-receptors. In dissociated cortical neurons, PS attenuated AMPA-induced inward currents whereas pregnenolone and PHS exhibited no significant effect. Thus, with strict structural specificity, PS but not pregnenolone or PHS attenuates AMPA cytotoxicity, probably by inhibiting activities of AMPA receptor-associated channels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2329-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15932592-Animals, pubmed-meshheading:15932592-Cerebral Cortex, pubmed-meshheading:15932592-Drug Interactions, pubmed-meshheading:15932592-Drug Synergism, pubmed-meshheading:15932592-Enzyme Inhibitors, pubmed-meshheading:15932592-Estrone, pubmed-meshheading:15932592-Excitatory Amino Acid Agonists, pubmed-meshheading:15932592-Membrane Potentials, pubmed-meshheading:15932592-Neurons, pubmed-meshheading:15932592-Neuroprotective Agents, pubmed-meshheading:15932592-Organ Culture Techniques, pubmed-meshheading:15932592-Pregnenolone, pubmed-meshheading:15932592-Rats, pubmed-meshheading:15932592-Rats, Wistar, pubmed-meshheading:15932592-Receptors, AMPA, pubmed-meshheading:15932592-Steryl-Sulfatase, pubmed-meshheading:15932592-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
pubmed:year
2005
pubmed:articleTitle
Pregnenolone sulphate attenuates AMPA cytotoxicity on rat cortical neurons.
pubmed:affiliation
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't