Source:http://linkedlifedata.com/resource/pubmed/id/20681583
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
16
|
| pubmed:dateCreated |
2010-8-19
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| pubmed:abstractText |
Marine organisms have yielded a variety of metabolites with neuropharmacological applications. Here we describe the isolation and pharmacological characterization of four novel, neurologically active purines 1-4, isolated from Haplosclerida sponges collected in the Republic of Palau. The structures were determined by analyses of spectral and X-ray data. Compound 1 induced convulsions upon intracerebroventricular injection into mice, with a CD50 value of 2.4 nmol/mouse. Purines 2-4 were active in mouse bioassays at higher doses. The seizurogenic activity of 1 was correlated with inhibition of neuronal GABAergic transmission, with only a modest impact on excitatory signaling, in electrophysiological recordings from hippocampal neurons. Despite having a purine template structure, the inhibitory activity of 1 was not prevented by a nonselective adenosine receptor antagonist. Thus, 1 represents a novel substituted purine that elicits convulsions through its actions on inhibitory neurotransmission. These 8-oxoisoguanine analogs comprise a new family of compounds closely related in structure to endogenous neurosignaling molecules and commonly used CNS stimulants.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1520-4804
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
26
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| pubmed:volume |
53
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6089-99
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| pubmed:meshHeading |
pubmed-meshheading:20681583-Action Potentials,
pubmed-meshheading:20681583-Animals,
pubmed-meshheading:20681583-Behavior, Animal,
pubmed-meshheading:20681583-Cells, Cultured,
pubmed-meshheading:20681583-Convulsants,
pubmed-meshheading:20681583-Crystallography, X-Ray,
pubmed-meshheading:20681583-Excitatory Postsynaptic Potentials,
pubmed-meshheading:20681583-Guanine,
pubmed-meshheading:20681583-Hippocampus,
pubmed-meshheading:20681583-Inhibitory Postsynaptic Potentials,
pubmed-meshheading:20681583-Magnetic Resonance Spectroscopy,
pubmed-meshheading:20681583-Mice,
pubmed-meshheading:20681583-Molecular Structure,
pubmed-meshheading:20681583-Neurons,
pubmed-meshheading:20681583-Palau,
pubmed-meshheading:20681583-Patch-Clamp Techniques,
pubmed-meshheading:20681583-Porifera,
pubmed-meshheading:20681583-Radioligand Assay,
pubmed-meshheading:20681583-Rats,
pubmed-meshheading:20681583-Rats, Sprague-Dawley,
pubmed-meshheading:20681583-Receptors, Cell Surface,
pubmed-meshheading:20681583-Synaptic Transmission
|
| pubmed:year |
2010
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| pubmed:articleTitle |
Novel N-methylated 8-oxoisoguanines from Pacific sponges with diverse neuroactivities.
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| pubmed:affiliation |
Faculty of Fisheries Sciences, Hokkaido University, Hakodate 041-8611, Japan.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|