MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guan, X. M.
Right arrow Articles by Kobilka, B. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guan, X. M.
Right arrow Articles by Kobilka, B. K.

Identification of a single amino acid residue responsible for the binding of a class of beta-adrenergic receptor antagonists to 5- hydroxytryptamine1A receptors

XM Guan, SJ Peroutka and BK Kobilka

Department of Neurology, Stanford University, California 94305.

The 5-hydroxytryptamine1A (5-HT1A) receptor can bind certain beta- adrenergic receptor antagonists, such as pindolol, with high affinity. Such pharmacological cross-reactivity suggests a structural similarity in the ligand binding site between the two receptors. To identify this structural entity, we mutated Asn385 in the seventh transmembrane domain of the human 5-HT1A receptor, based on the observation that this residue is conserved in all 5-HT1A and beta-adrenergic receptors of different species but is absent in all other cloned guanine nucleotide- binding protein-coupled receptors. This single point mutation (Asn385 to valine) causes a highly selective decrease in the affinity of pindolol and other aryloxyalkylamines for the mutant receptor (about 100-fold), while producing only minor changes in the binding of other 5- HT agonists and antagonists. The results provide direct evidence that Asn385 is responsible for the high affinity interaction between 5-HT1A receptors and aryloxyalkylamine beta-adrenergic antagonists but is not required for the binding of other chemical classes of ligands.

Volume 41, Issue 4, pp. 695-698, 04/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
M. L. Lopez-Rodriguez, B. Vicente, X. Deupi, S. Barrondo, M. Olivella, M. J. Morcillo, B. Behamu, J. A. Ballesteros, J. Salles, and L. Pardo
Design, Synthesis and Pharmacological Evaluation of 5-Hydroxytryptamine1a Receptor Ligands to Explore the Three-Dimensional Structure of the Receptor
Mol. Pharmacol., July 1, 2002; 62(1): 15 - 21.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. A. Ballesteros, L. Shi, and J. A. Javitch
Structural Mimicry in G Protein-Coupled Receptors: Implications of the High-Resolution Structure of Rhodopsin for Structure-Function Analysis of Rhodopsin-Like Receptors
Mol. Pharmacol., July 1, 2001; 60(1): 1 - 19.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
A. L. Gnagey, M. Seidenberg, and J. Ellis
Site-Directed Mutagenesis Reveals Two Epitopes Involved in the Subtype Selectivity of the Allosteric Interactions of Gallamine at Muscarinic Acetylcholine Receptors
Mol. Pharmacol., December 1, 1999; 56(6): 1245 - 1253.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
H. M. Zuurmond, J. Hessling, K. Blüml, M. Lohse, and A. P. Ijzerman
Study of Interaction between Agonists and Asn293 in Helix VI of Human beta 2-Adrenergic Receptor
Mol. Pharmacol., November 1, 1999; 56(5): 909 - 916.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. E. Elling, K. Thirstrup, B. Holst, and T. W. Schwartz
Conversion of agonist site to metal-ion chelator site in the beta 2-adrenergic receptor
PNAS, October 26, 1999; 96(22): 12322 - 12327.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. Kakoki, Y. Hirata, H. Hayakawa, H. Nishimatsu, Y. Suzuki, D. Nagata, E. Suzuki, K. Kikuchi, T. Nagano, and M. Omata
Effects of Vasodilatory ß-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney
Hypertension, January 1, 1999; 33(1): 467 - 471.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. J. Barr and D. R. Manning
Agonist-independent Activation of Gz by the 5-Hydroxytryptamine1A Receptor Co-expressed in Spodoptera frugiperda Cells. DISTINGUISHING INVERSE AGONISTS FROM NEUTRAL ANTAGONISTS
J. Biol. Chem., December 26, 1997; 272(52): 32979 - 32987.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
W. Kuipers, R. Link, P. J. Standaar, A. R. Stoit, I. Van Wijngaarden, R. Leurs, and A. P. Ijzerman
Study of the Interaction Between Aryloxypropanolamines and Asn386 in Helix VII of the Human 5-Hydroxytryptamine1A Receptor
Mol. Pharmacol., May 1, 1997; 51(5): 889 - 896.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. D. Jensen, F. Guarnieri, S. G. F. Rasmussen, F. Asmar, J. A. Ballesteros, and U. Gether
Agonist-induced Conformational Changes at the Cytoplasmic Side of Transmembrane Segment 6 in the beta 2 Adrenergic Receptor Mapped by Site-selective Fluorescent Labeling
J. Biol. Chem., March 16, 2001; 276(12): 9279 - 9290.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. J. Waugh, R. J. Gaivin, M. J. Zuscik, P. Gonzalez-Cabrera, S. A. Ross, J. Yun, and D. M. Perez
Phe-308 and Phe-312 in Transmembrane Domain 7 Are Major Sites of alpha 1-Adrenergic Receptor Antagonist Binding. IMIDAZOLINE AGONISTS BIND LIKE ANTAGONISTS
J. Biol. Chem., June 29, 2001; 276(27): 25366 - 25371.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics