Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2000-1-13
pubmed:abstractText
The 5-HT1A receptor is implicated in depression and anxiety. This receptor couples to G(i) proteins to inhibit adenylyl cyclase (AC) activity but can stimulate AC in tissues (e.g. hippocampus) that express ACII. The role of ACII in receptor-mediated stimulation of cAMP formation was examined in HEK-293 cells transfected with the 5-HT1A receptor, which mediated inhibition of basal and G(s)-induced cAMP formation in the absence of ACII. In cells cotransfected with 5-HT1A receptor and ACII plasmids, 5-HT1A agonists induced a 1. 5-fold increase in cAMP level. Cotransfection of 5-HT1A receptor, ACII, and Galpha(i2), but not Galpha(i1), Galpha(i3), or Galpha(o), resulted in an agonist-independent 6-fold increase in the basal cAMP level, suggesting that G(i2) preferentially coupled the receptor to ACII. The 5-HT1B receptor also constitutively activated ACII. Constitutive activity of the 5-HT1A receptor was blocked by pertussis toxin and the Gbetagamma antagonist, betaCT, suggesting an important role for Gbetagamma-mediated activation of ACII. The Thr-149 --> Ala mutation in the second intracellular domain of the 5-HT1A receptor disrupted Gbetagamma-selective activation of ACII. Spontaneous 5-HT1A receptor activity was partially attenuated by 5-HT1A receptor partial agonists with anxiolytic activity (e.g. buspirone and flesinoxan) but was not altered by full agonists or antagonists. Thus, anxiolytic activity may involve inhibition of spontaneous 5-HT1A receptor activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase, http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Buspirone, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha..., http://linkedlifedata.com/resource/pubmed/chemical/HTR1B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Spiperone, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35469-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10585418-Adenylate Cyclase, pubmed-meshheading:10585418-Adenylate Cyclase Toxin, pubmed-meshheading:10585418-Buspirone, pubmed-meshheading:10585418-Cell Line, pubmed-meshheading:10585418-Cyclic AMP, pubmed-meshheading:10585418-Dopamine, pubmed-meshheading:10585418-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:10585418-Humans, pubmed-meshheading:10585418-Isoenzymes, pubmed-meshheading:10585418-Kidney, pubmed-meshheading:10585418-Kinetics, pubmed-meshheading:10585418-Pertussis Toxin, pubmed-meshheading:10585418-Receptor, Serotonin, 5-HT1B, pubmed-meshheading:10585418-Receptors, Serotonin, pubmed-meshheading:10585418-Receptors, Serotonin, 5-HT1, pubmed-meshheading:10585418-Recombinant Proteins, pubmed-meshheading:10585418-Serotonin Antagonists, pubmed-meshheading:10585418-Serotonin Receptor Agonists, pubmed-meshheading:10585418-Spiperone, pubmed-meshheading:10585418-Transfection, pubmed-meshheading:10585418-Virulence Factors, Bordetella
pubmed:year
1999
pubmed:articleTitle
Constitutive G(i2)-dependent activation of adenylyl cyclase type II by the 5-HT1A receptor. Inhibition by anxiolytic partial agonists.
pubmed:affiliation
Neuroscience Research Institute, Department of Medicine, University of Ottawa, Ottawa, Canada K1H 8M5. palbert@uottawa.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't