ADRB - Adrenergic receptor Beta | Elisa - Clia - Antibody - Protein

Background

Adrenergic receptors (ADRB) are a class of G protein-coupled receptors that respond to the neurotransmitter and hormone adrenaline (epinephrine) and noradrenaline (norepinephrine). There are two main subtypes of adrenergic receptors: alpha-adrenergic receptors and beta-adrenergic receptors. Beta-adrenergic receptors are further divided into three subtypes: β1, β2, and β3. β1-adrenergic receptors: are predominantly found in the heart (myocardium), where they regulate heart rate and contractility.β2-adrenergic receptors are found in various tissues, including smooth muscle cells in the lungs (bronchioles), blood vessels, and skeletal muscle, as well as in liver and pancreas. They regulate bronchodilation, vasodilation, glycogenolysis, and insulin secretion.β3-adrenergic receptors: found in adipose tissue and the urinary bladder. They play a role in lipolysis (breakdown of fats) and relaxation of bladder smooth muscle. β1-adrenergic receptors in the heart increase heart rate (positive chronotropic effect) and contractility (positive inotropic effect) in response to adrenaline and noradrenaline. These effects help to increase cardiac output in fight-or-flight responses.β2-adrenergic receptors in the lungs cause relaxation of bronchial smooth muscles, leading to bronchodilation and increased airflow. This effect is beneficial in the treatment of asthma and other respiratory conditions.β2-adrenergic receptors in blood vessels, particularly in skeletal muscle, mediate vasodilation, leading to increased blood flow and oxygen delivery to active tissues. β-adrenergic receptors, particularly β3-adrenergic receptors in adipose tissue, stimulate lipolysis, the breakdown of stored fat, releasing free fatty acids into the bloodstream. This can provide energy substrates during times of stress or exercise. β3-adrenergic receptors in the urinary bladder mediate relaxation of the detrusor muscle, increasing bladder capacity and reducing urgency.

Protein Structure

Beta-adrenergic receptors share a common structure typical of GPCRs:

• Seven Transmembrane Domains: Characteristic of GPCRs, these domains span the cell membrane.
• Extracellular N-terminus: Important for ligand binding.
• Intracellular C-terminus: Involved in signaling and interaction with G proteins and other intracellular molecules.
• Ligand Binding Site: Located within the transmembrane regions.

Classification and Subtypes

The ADRB family consists of three subtypes based on their gene encoding and tissue distribution:

• ADRB1: Encodes the β1-adrenergic receptor, primarily found in the heart, kidneys, and adipose tissue.
• ADRB2: Encodes the β2-adrenergic receptor, predominantly expressed in the lungs, vascular smooth muscle, and skeletal muscle.
• ADRB3: Encodes the β3-adrenergic receptor, mainly located in adipose tissue and involved in metabolic regulation.

Function and Biological Significance

Beta-adrenergic receptors mediate various physiological responses through their interaction with Gs proteins, leading to the activation of adenylate cyclase and increased cyclic AMP (cAMP) levels:

1. Cardiac Function: β1-ARs increase heart rate and contractility, enhancing cardiac output.
2. Smooth Muscle Relaxation: β2-ARs cause relaxation of smooth muscle in the airways (bronchodilation) and blood vessels (vasodilation).
3. Metabolic Regulation: β3-ARs are involved in lipolysis and thermogenesis in adipose tissue.

Interactions

1. Gs Proteins: Upon activation, β-ARs interact with Gs proteins, leading to the activation of adenylate cyclase.
2. Adenylate Cyclase: Activation of this enzyme results in increased cAMP production, which activates protein kinase A (PKA).
3. PKA and Downstream Effectors: PKA phosphorylates various target proteins, leading to cellular responses such as increased heart rate, smooth muscle relaxation, and metabolic changes.

Clinical Significance

1. Cardiovascular Diseases: Beta-blockers, which are antagonists of β-ARs, are commonly used to treat hypertension, angina, and heart failure by reducing heart rate and contractility.
2. Asthma and COPD: β2-AR agonists, such as albuterol, are used as bronchodilators to manage asthma and chronic obstructive pulmonary disease (COPD).
3. Obesity: β3-AR agonists are being explored for their potential to enhance lipolysis and thermogenesis in the treatment of obesity.
4. Hyperthyroidism: Beta-blockers are used to manage symptoms of hyperthyroidism, such as tachycardia and tremors.

Summary

Beta-adrenergic receptors (β-ARs), including subtypes β1, β2, and β3, are GPCRs that mediate critical physiological responses through interaction with catecholamines. They activate Gs proteins, leading to the activation of adenylate cyclase and increased cAMP levels, which in turn activates PKA and various downstream effectors. β1-ARs are primarily involved in cardiac function, β2-ARs in smooth muscle relaxation, and β3-ARs in metabolic regulation. Clinically, β-ARs are significant in the management of cardiovascular diseases, asthma, COPD, and obesity. Understanding the roles and mechanisms of β-ARs is essential for developing therapeutic strategies targeting these receptors.