Disease relevance of ADRB2

• The increase in heart rate was not due to direct stimulation of cardiac beta 1-adrenoceptors by clenbuterol but was consistent with a reflex response to beta 2-adrenoceptor-mediated hypotension [1].
• Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating bronchospasm and alleviating the symptoms of chronic obstructive pulmonary disease (COPD) in the horse [2].
• The effect of a selective beta 2-adrenoceptor agonist on basal volume and on insulin-, 2-deoxy-D-glucose (2-DG)-, and food-induced gastrin release was studied in conscious gastric fistula dogs [3].

High impact information on ADRB2

• The ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the beta2-adrenergic receptor (beta2AR). beta2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin [4].
• When this clone was inserted into a mammalian expression vector and transfected into COS-7 cells, a protein that specifically phosphorylated the agonist-occupied form of the beta 2-adrenergic receptor and phosphorylated, much more weakly, the light-bleached form of rhodopsin was expressed [5].
• Unlike native protein, upon agonist activation, this mutant arrestin3 expressed in COS1 cells neither supported beta2-adrenergic receptor internalization nor did it concentrate in coated pits, although it was recruited to the plasma membrane [6].
• Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM) [7].
• Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1 [8].

Biological context of ADRB2

• Complementary DNA cloning gave use to the first full-length bovine beta2-adrenoceptor messenger RNA sequence (2030 bases) [9].
• Genetic mapping of the ADRB2 gene on cattle chromosome 7 [10].
• 4. In the trachea, a beta 2-predominant tissue, betaxolol and atenolol were more selective for beta 1-adrenoceptor binding sites than beta 2-adrenoceptor binding sites, whereas ICI-118551 and butoxamine were more selective for beta 2-adrenoceptor binding sites [11].
• Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor [4].
• The amino acid sequence deduced from the beta-AR gene reveals homology with the visual pigment rhodopsin of retinal rod outer segments [12].

Anatomical context of ADRB2

• After progesterone supplementation, oviduct epithelial cells showed elevated receptor expression in culture, supporting the hypothesis that progesterone up-regulates the beta2-adrenergic receptor within these cells [9].
• Spasmogen-stimulated phosphoinositide hydrolysis represents one of the major signalling pathways mediating pharmacomechanical coupling in airways smooth muscle (ASM), and cyclic AMP-induced inhibition of phosphoinositidase C has been proposed as an important mechanism underlying the bronchodilator properties of beta2-adrenoceptor agonists [13].
• We determined if decreases in relative free intracellular calcium concentration ([Ca2+]i) caused by salbutamol, a selective beta2-adrenoreceptor agonist, were paralleled by calcium egression from the cytosol in bovine trachealis muscle strips [14].
• These results confirmed the presence of postjunctional beta 1- and beta 2-adrenoceptor subtypes in lymphatic vessels and provide the first indication of the existence of two pharmacologically and functionally distinct cell populations, one of which exhibits pacemaker activity [15].
• Alpha1c- and beta2-adrenergic receptor mRNA distribution in the bovine mammary gland detected by competitive RT-PCR [16].

Associations of ADRB2 with chemical compounds

• Hence, the widely used beta 2-adrenoceptor agonists, salbutamol and salmeterol, are able to reduce endothelial permeability at nanomolar concentrations [17].
• Cardiovascular effects of clenbuterol are beta 2-adrenoceptor-mediated in steers [1].
• The beta 2-adrenergic receptor (beta-AR) is an integral membrane glycoprotein of apparent Mr approximately equal to 64,000 [12].
• From the established equations it is concluded that the phenoxypropanolamine derivatives bind to the beta 2-adrenoceptor in a way different from that of the ligands in both ethanolamine classes [18].
• Neither the spasmolytic nor anti-spasmogenic effects of AH 21-132 were antagonized by the beta 2-adrenoceptor blocking drug ICI 118551 (50 nM) [19].

Regulatory relationships of ADRB2

• The expressed kinases were fully active as evidenced by their ability to specifically phosphorylate the agonist-occupied beta 2-adrenergic receptor (beta 2AR) and light-activated rhodopsin [20].

Other interactions of ADRB2

• GRK5 phosphorylation of rhodopsin or beta 2-adrenergic receptor is not stimulated by G protein beta gamma-subunits [21].

Analytical, diagnostic and therapeutic context of ADRB2

• Quantitative evaluation of the beta 2-adrenoceptor intrinsic activity of N-tert-butylphenylethanolamines [22].

References