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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1990-12-10
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pubmed:abstractText |
We have previously shown that chronic administration of the 5-hydroxytryptamine (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 5-HT2 receptor number in rat cerebral cortex. This study investigates the effects of acute and chronic ritanserin administration, on 5-HT2 receptor linked inositol phospholipid hydrolysis in rat cortical slices and compares it with the effect of a chronic clorgyline regimen. [3H]Myo-inositol (50 microCi) was used to label inositol phospholipids. Their subsequent hydrolysis in the presence or absence of 5-HT was determined by the accumulation of [3H]myoinositol monophosphate ([3H]InsP). Addition of 5 nM ritanserin to slices had no effect on basal or 5-HT stimulated [3H]InsP accumulation whereas 100 nM ritanserin blocked the stimulated response by 65%. Acutely, ritanserin (15 mg/kg i.p.) completely blocked 5-HT stimulated [3H]InsP accumulation. Chronic ritanserin or clorgyline treatment had no effect on basal levels of [3H]InsP accumulation compared to controls (mean value 3125 +/- 298 dpm/mg protein). Ritanserin increased 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT and this effect was significant at 100 microM 5-HT. Clorgyline had no significant or consistent effect on 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT. Thus the effects of both chronic clorgyline and ritanserin administration on 5-HT2 linked inositol phospholipid hydrolysis do not correlate with their effects on 5-HT2 receptor number (Bmax). The situation is further complicated since ritanserin significantly increases phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) labelling whereas clorgyline significantly increases PtdIns and PtdIns4P labelling. The implications of this are discussed.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Clorgyline,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Ritanserin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2111-6
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:2122900-Animals,
pubmed-meshheading:2122900-Cerebral Cortex,
pubmed-meshheading:2122900-Clorgyline,
pubmed-meshheading:2122900-Hydrolysis,
pubmed-meshheading:2122900-Phosphatidylinositols,
pubmed-meshheading:2122900-Piperidines,
pubmed-meshheading:2122900-Rats,
pubmed-meshheading:2122900-Rats, Inbred Strains,
pubmed-meshheading:2122900-Receptors, Serotonin,
pubmed-meshheading:2122900-Ritanserin,
pubmed-meshheading:2122900-Serotonin,
pubmed-meshheading:2122900-Serotonin Antagonists
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pubmed:year |
1990
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pubmed:articleTitle |
The effect of chronic ritanserin and clorgyline administration on 5-HT2 receptor linked inositol phospholipid hydrolysis.
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pubmed:affiliation |
Department of Neuroscience, Institute of Psychiatry, London, U.K.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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