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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-11-22
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pubmed:abstractText |
1. A number of compounds, including the selective 5-HT7 receptor antagonist SB-258719, were investigated for their effect on [3H]-5-carboxamidotryptamine (5-CT) radioligand binding and 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes, in order to confirm the presence of functionally coupled 5-HT7 receptors in this tissue. 2. The [3H]-5-CT radioligand binding profile was consistent with binding predominantly to 5-HT7 receptors. The affinity of SB-258719 (pKi 7.2+/-0.1) was similar to its reported human 5-HT7 receptor affinity. 3. In the adenylyl cyclase functional assay, 5-CT was a potent and full agonist compared to 5-HT, whereas 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) was a partial agonist (intrinsic activity 0.4+/-0.1). The rank order of potency for agonists (5-CT>5-HT approximately 8-OH-DPAT) was consistent with activation of 5-HT7 receptors. SB-258719 (5 microM) and methiothepin (1 microM) surmountably antagonized the response to 5-CT, consistent with competitive antagonism. The pKB for SB-258719 (7.2+/-0.1) was in good agreement with its reported antagonist potency at the human cloned 5-HT7 receptor. 4. In the functional assay, WAY-100635 (100 nM) and cyanopindolol (1 microM) induced a biphasic 5-CT response curve, consistent with selective antagonism of a component of the response to 5-CT. The estimated pKB values for WAY-100635 and cyanopindolol (9.6 and 8.4 respectively) were in good agreement with their reported 5-HT1A receptor affinities. 5. The data are consistent with the presence of 5-HT7 receptors in guinea-pig hippocampus which are positively coupled to adenylyl cyclase. In addition, 5-HT7 receptor-mediated stimulation of adenylyl cyclase activity in this tissue appears to be augmented by a mechanism involving 5-HT1A receptor activation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-1533220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-1655150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-1962211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-2849052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-2941565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-2945992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-2952874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-3207999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-4202581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-7518496,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-7647964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-7938165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-8226867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-8358562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-8398139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-8788530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-9298538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-9513592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10498847-9720804
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-carboxamidotryptamine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/serotonin 7 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
128
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
158-64
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10498847-Adenylate Cyclase,
pubmed-meshheading:10498847-Animals,
pubmed-meshheading:10498847-Binding, Competitive,
pubmed-meshheading:10498847-Cell Membrane,
pubmed-meshheading:10498847-Enzyme Activation,
pubmed-meshheading:10498847-Guinea Pigs,
pubmed-meshheading:10498847-Hippocampus,
pubmed-meshheading:10498847-Male,
pubmed-meshheading:10498847-Receptors, Serotonin,
pubmed-meshheading:10498847-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:10498847-Serotonin,
pubmed-meshheading:10498847-Serotonin Antagonists,
pubmed-meshheading:10498847-Serotonin Receptor Agonists
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pubmed:year |
1999
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pubmed:articleTitle |
5-CT stimulation of adenylyl cyclase activity in guinea-pig hippocampus: evidence for involvement of 5-HT7 and 5-HT1A receptors.
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pubmed:affiliation |
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW. David _R_Thomas@sbphrd.com
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pubmed:publicationType |
Journal Article
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