[Beta-adrenergic receptors of the normal heart and in heart failure].
The heart is often refereed to as an "beta-adrenergic organ" because beta-adrenergic agonists are powerful stimulants of cardiac contractility. Catecholamines acting through beta-adrenoceptors produce both positive inotropic and chronotropic effects in human heart. It is now generally accepted that in human heart both beta 1- and beta 2-adrenoceptors coexist. beta-Adrenergic transduction system consist of membrane-bound beta-receptors, the effector enzyme adenylyl cyclase and guanine nucleotide-binding transduction (G) proteins. Repeated long-lasting agonist stimulus evokes homologous or heterologous desensitization of transduction system. Chronic heart failure accompanies with decreased responsiveness to beta-adrenoceptor agonists and is thought to exacerbate the loss of cardiac contractility. Depending on the etiology of heart failure abnormalities of the beta-receptor-G protein-adenylyl cyclase system result from a reduced of beta 1-receptors, uncoupling of beta 1- or beta 2-receptors, alteration of G-protein function, or decreased catalytic subunit activity of adenylyl cyclase and enhanced expression of beta-adrenoceptor kinase. The model most widely used is that of circulating lymphocytes that contain a homogeneous population of beta 2-adrenoceptors. The biochemical and pharmacological properties of human lymphocyte beta 2-adrenoceptors are quite comparable to those of heart beta 2-receptors. The analysis of lymphocyte beta 2-adrenoceptor-adenylyl cyclase system can be used as a model for long-term regulation of human cardiac beta 1- and beta 2-adrenoceptors only if serial changes in response to administration of non-selective beta-adrenergic agonists or antagonists are being investigated. This review concentrates on beta-adrenoceptors in human healthy heart and in heart failure and also on lymphocyte beta 2-adrenoceptors and on the changes of these receptors properties under the influence of some cardiotropic drugs.
Krasnikov
T L
TL
Russian Cardiology Research Complex, Ministry of Health, Moscow.
Gabrusenko
S A
SA
D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins