Pharmacogenetics of beta-1-beta- and 2-adrenergic receptors

被引:108
作者
Liggett, SB
机构
[1] Univ Cincinnati, Coll Med, Dept Med, Cincinnati, OH USA
[2] Univ Cincinnati, Coll Med, Dept Mol Genet, Cincinnati, OH USA
[3] Univ Cincinnati, Coll Med, Dept Pharmacol, Cincinnati, OH USA
关键词
beta-agonist; adenylyl cyclase; desensitization; G protein; tachyphylaxis; heart failure; asthma; polymorphism;
D O I
10.1159/000028397
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
beta(1)- and beta(2)-adrenergic receptors are G protein-coupled receptors expressed throughout the body and serve as receptors for the catecholamines epinephrine and norepinephrine. They are targets for therapeutive agonists and/or antagonists in treatment of heart failure and asthma. Nonsynonymous coding and promoter polymorphisms of both receptors have been identified in the general population. These have been mimicked in transfected cell systems and transgenic mice, and show altered expression, ligand binding, coupling, or regulation phenotypes, Clinical studies to date have revealed that some of these polymorphisms have a significant disease modifying effect or alter the response to treatment. These are some of the first G protein coupled receptor polymorphisms to undergo extensive in vitro study and clinical validation; there are likely to be polymorphisms of other receptors of the superfamily that will have clinical relevance as well, Copyright(C)2000S.KargerAG,Basel.
引用
收藏
页码:167 / 173
页数:7
相关论文
共 31 条
[1]   Comparison of regularly scheduled with as-needed use of albuterol in mild asthma [J].
Drazen, JM ;
Israel, E ;
Boushey, HA ;
Chinchilli, VM ;
Fahy, JV ;
Fish, JE ;
Lazarus, SC ;
Lemanske, RF ;
Martin, RJ ;
Peters, SP ;
Sorkness, C ;
Szefler, SJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (12) :841-847
[2]  
DRYSDALE CM, 2000, IN PRESS P NATL ACAD
[3]   AMINO-TERMINAL POLYMORPHISMS OF THE HUMAN BETA(2)-ADRENERGIC RECEPTOR IMPART DISTINCT AGONIST-PROMOTED REGULATORY PROPERTIES [J].
GREEN, SA ;
TURKI, J ;
INNIS, M ;
LIGGETT, SB .
BIOCHEMISTRY, 1994, 33 (32) :9414-9419
[4]  
GREEN SA, 1993, J BIOL CHEM, V268, P23116
[5]   INFLUENCE OF BETA(2)-ADRENERGIC RECEPTOR GENOTYPES ON SIGNAL-TRANSDUCTION IN HUMAN AIRWAY SMOOTH-MUSCLE CELLS [J].
GREEN, SA ;
TURKI, J ;
BEJARANO, P ;
HALL, IP ;
LIGGETT, SB .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 13 (01) :25-33
[6]   ASSOCIATION OF GLU-27 BETA(2)-ADRENOCEPTOR POLYMORPHISM WITH LOWER AIRWAY REACTIVITY IN ASTHMATIC SUBJECTS [J].
HALL, IP ;
WHEATLEY, A ;
WILDING, P ;
LIGGETT, SB .
LANCET, 1995, 345 (8959) :1213-1214
[7]  
Hancox RJ, 1998, EUR RESPIR J, V11, P589
[8]   β2-Adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals [J].
Hoit, BD ;
Suresh, DP ;
Craft, L ;
Walsh, RA ;
Liggett, SB .
AMERICAN HEART JOURNAL, 2000, 139 (03) :537-542
[9]  
ISRAEL E, 2000, IN PRESS AM J RESP C
[10]   Essential hypertension in African Caribbeans associates with a variant of the beta(2)-adrenoceptor [J].
Kotanko, P ;
Binder, A ;
Tasker, J ;
DeFreitas, P ;
Kamdar, S ;
Clark, AJL ;
Skrabal, F ;
Caulfield, M .
HYPERTENSION, 1997, 30 (04) :773-776