Biomaterial Database

The beta-adrenergic receptors. 2002

Gerd Wallukat

Max Delbrück Centrum for Moleculare Medicine, Berlin, Germany. gwalluk@mdc-berlin.de

BACKGROUND The beta-adrenergic receptors of the myocardium play an important role in the regulation of heart function. The beta-adrenergic receptors belong to the family of G-protein coupled receptors. Three subtypes have been distinguished (beta1-, beta2-, and beta3-adrenoceptors). The receptors consist of seven membrane-spanning domains, three intra- and three extracellular loops, one extracellular N-terminal domain, and one intracellular C-terminal tail. METHODS Stimulation of beta-adrenergic receptors by catecholamines is realized via the beta-adrenoceptor-adenylylcyclase-protein kinase A cascade. The second messenger is the cyclic AMP (cAMP). Stimulation of the cascade caused an accumulation of the second messenger cAMP and activated via the cAMP the cAMP dependent protein kinase A (PKA) The PKA phosphorylated, beside other cell proteins, the beta-adrenergic receptors. A phosphorylation of the beta-adrenergic receptors caused - with exception of the beta3-adrenoceptor - an uncoupling and desensitisation of the receptors. Phosphorylation via the G-protein receptor kinase (GRK or betaARK) also caused uncoupling and reduced the beta-adrenergic responsiveness. The uncoupling of the receptor is the prerequisite for receptor internalisation. In the process of internalisation the receptor shifted from the sarcolemma membrane into cytosolic compartments. Chronic beta-adrenergic stimulation caused a down-regulation of the receptors. During this process of desensitisation the expression of the receptor on mRNA and protein level is reduced. In patients with dilated cardiomyopathy the beta-adrenergic responsiveness of the myocardium is diminished. It was shown that in these patients the expression of the beta1-adrenergic receptor is reduced on the mRNA and protein level. In these patients the expression of the inhibitory G-protein G(i) is increased. Furthermore, the expression of the G-protein receptor kinase is elevated. This kinase induces the uncoupling of the beta-adrenergic receptors. These alterations of the beta-adrenoceptor signal cascade may be induced by an elevated catecholamine release or by agonist-like autoantibodies directed against the beta1-adrenergic receptor found in patients with dilated cardiomyopathy. Both, permanent stimulation with catecholamines and chronic treatment with agonistic anti-beta1-adrenoceptor autoantibodies cause a reduction of the expression of the beta1-adrenoceptor on mRNA and protein level in "in vitro" experiments. Moreover, an over-expression of the beta1-adrenoceptor, the stimulatory G(s) protein, and the protein kinase A induce detrimental alterations of the cardiac function and morphology in transgenic animals. These animals developed heart failure accompanied by an increased mortality rate.

UI	MeSH Term	Description	Entries
D007074	Immunoglobulin G	The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.	Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D011943	Receptors, Adrenergic, beta	One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.	Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002311	Cardiomyopathy, Dilated	A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.	Cardiomyopathy, Congestive,Congestive Cardiomyopathy,Dilated Cardiomyopathy,Cardiomyopathy, Dilated, 1a,Cardiomyopathy, Dilated, Autosomal Recessive,Cardiomyopathy, Dilated, CMD1A,Cardiomyopathy, Dilated, LMNA,Cardiomyopathy, Dilated, With Conduction Defect 1,Cardiomyopathy, Dilated, with Conduction Deffect1,Cardiomyopathy, Familial Idiopathic,Cardiomyopathy, Idiopathic Dilated,Cardiomyopathies, Congestive,Cardiomyopathies, Dilated,Cardiomyopathies, Familial Idiopathic,Cardiomyopathies, Idiopathic Dilated,Congestive Cardiomyopathies,Dilated Cardiomyopathies,Dilated Cardiomyopathies, Idiopathic,Dilated Cardiomyopathy, Idiopathic,Familial Idiopathic Cardiomyopathies,Familial Idiopathic Cardiomyopathy,Idiopathic Cardiomyopathies, Familial,Idiopathic Cardiomyopathy, Familial,Idiopathic Dilated Cardiomyopathies,Idiopathic Dilated Cardiomyopathy
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004622	Embryo, Mammalian	The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.	Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic