Linked Life Data

11414657

Source:http://linkedlifedata.com/resource/pubmed/id/11414657

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-20
pubmed:abstractText
Serotonin (5-hydroxytryptamine, 5-HT) receptor pre-mRNA is alternatively spliced in human tissue to produce three splice variants, h5-HT7(a), h5-HT7(b) and h5-HT7(d), which differ only in their carboxyl terminal tails. Using membranes from transiently and stably transfected HEK293 cells expressing the three recombinant h5-HT7 splice variants we compared their pharmacological profiles and ability to activate adenylyl cyclase. Using PCR on cDNA derived from various human tissues, the 5-HT7(a) and 5-HT7(b) splice variants were detected in every tissue examined. The h5-HT7(d) splice variant was detected in 13 of 16 tissues examined, with predominant expression in the heart, small intestine, colon, ovary and testis. All three h5-HT7 splice variants displayed high affinity binding for [3H]5-HT (pKd=8.8-8.9) in the presence and absence of 100 microM GTP and had similar binding affinities for all 17 ligands evaluated. In HEK293 cells expressing similar, high levels of receptor (approximately 10,000 fmol/mg protein), 5-CT (5-carboxamidotryptamine), 5-MeOT (5-methoxytryptamine) and 5-HT were full agonists while 8-OH-DPAT ((2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin) was a partial agonist with relative efficacy of approximately 0.8. Even at this high receptor level, EC50 values for stimulation of adenylyl cyclase were 10- to 50-fold higher than the Kd values, indicating a lack of spare receptors. No significant differences in coupling to adenylyl cyclase were observed between the three splice variants over a wide range of receptor expression levels. For antagonists, binding affinities determined by displacement of [3H]5-HT binding and by competitive inhibition of 5-HT-stimulated adenylyl cyclase activity were essentially identical amongst the splice variants. These studies indicate that the three human splice variants are pharmacologically indistinguishable and that modifications of the carboxyl tail do not influence coupling to adenylyl cyclase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
363
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
620-32
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution.
pubmed:affiliation
MSD Cardiovascular Research Center, Rikshospitalet University Hospital and Department of Pharmacology, University of Oslo, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't