Source:http://linkedlifedata.com/resource/pubmed/id/17260949
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2007-1-30
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pubmed:abstractText |
The competitive antagonist d-tubocurarine (curare) has greater potency at mouse than at human 5-hydroxytryptamine 3A (5-HT3A) receptors, despite 84% amino acid sequence identity between the receptors. Within the ligand binding domain of this receptor are six loops (A-F). A previous report demonstrated that loop C of the 5-HT3A receptor contributed to differential potency between the receptors [Hope, A. G. et al. (1999) Mol. Pharmacol. 55, 1037-1043]. The present study tested the hypothesis that loop F plays a significant role in conferring interspecies curare potency differences. Wild-type, chimeric, and point mutant 5-HT3A receptors were expressed in Xenopus oocytes, and two-electrode voltage clamp electrophysiological recordings were performed. Our data suggest that loops C and F contribute to curare potency, given that the curare IC50's (concentration of drug that produces 50% inhibition of the response) for chimeric human receptors with substitutions of mouse residues in loop C (40.07 +/- 2.52 nM) or loop F (131.8 +/- 5.95 nM) were intermediate between those for the mouse (12.99 +/- 0.77 nM) and human (1817 +/- 92.36 nM) wild-type receptors. Two human point mutant receptors containing mouse receptor substitutions in loop F (H-K195E or H-V202I) had significantly lower curare IC50's than that of the human receptor. The human double mutant receptor, H-K195E,V202I, had the same curare IC50 (133.8 +/- 6.38 nM) as that of the human receptor containing all six loop F mouse substitutions. These results demonstrate that two loop F residues make a significant contribution in determining curare potency at the 5-HT3A receptor.
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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/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/HTR3A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Htr3a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Neuromuscular Nondepolarizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT3,
http://linkedlifedata.com/resource/pubmed/chemical/Tubocurarine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1194-204
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17260949-Amino Acids,
pubmed-meshheading:17260949-Animals,
pubmed-meshheading:17260949-Binding Sites,
pubmed-meshheading:17260949-Electrophysiology,
pubmed-meshheading:17260949-Humans,
pubmed-meshheading:17260949-Inhibitory Concentration 50,
pubmed-meshheading:17260949-Mice,
pubmed-meshheading:17260949-Neuromuscular Nondepolarizing Agents,
pubmed-meshheading:17260949-Oocytes,
pubmed-meshheading:17260949-Point Mutation,
pubmed-meshheading:17260949-Receptors, Serotonin,
pubmed-meshheading:17260949-Receptors, Serotonin, 5-HT3,
pubmed-meshheading:17260949-Species Specificity,
pubmed-meshheading:17260949-Transduction, Genetic,
pubmed-meshheading:17260949-Tubocurarine,
pubmed-meshheading:17260949-Xenopus
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pubmed:year |
2007
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pubmed:articleTitle |
The role of loop F residues in determining differential d-tubocurarine potencies in mouse and human 5-hydroxytryptamine 3A receptors.
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pubmed:affiliation |
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 Fourth Street, Lubbock, Texas 79430, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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