The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).
Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupils of the eye, mobilizing energy, and diverting blood flow from non-essential organs to skeletal muscle.
History
By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different effects on body tissues, depending on the conditions of stimulation (such as the presence or absence of some toxin). Over the first half of the 20th century, two main proposals were made to explain this phenomenon:
The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that interacts with (binds) epinephrine, a hormone and neurotransmitter (ligand synonym, adrenaline) whose signaling, via a downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation. Unlike other adrenergic receptors, norepinephrine does not produce β2 receptor stimulation.
The official symbol for the human gene encoding the β2 adrenoreceptor is ADRB2.
Gene
The ADRB2 gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity and type 2 diabetes.
Structure
The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined by making a fusion protein with lysozyme to increase the hydrophilic surface area of the protein for crystal contacts.
The beta-1 adrenergic receptor (β1 adrenoreceptor), also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein and is expressed predominantly in cardiac tissue.
Receptor
Actions
Actions of the β1 receptor include:
- Increase heart rate in sinoatrial node (SA node) (chronotropic effect)
- Increase atrial cardiac muscle contractility. (inotropic effect)
- Increases contractility and automaticity of ventricular cardiac muscle.
- Increases conduction and automaticity of atrioventricular node (AV node)
The interferon-α/β receptor (IFNAR) is a receptor which binds type I interferons including interferon-α and -β. It is a heteromeric cell surface receptor composed of one chain with two subunits referred to as IFNAR1 and IFNAR2. Upon binding of type I IFNs, IFNAR activates the JAK-STAT signaling pathway. Interferon stimulation classically results in an anti-viral immune response.
Structure
The structure was obtained using NMR. Originally 35 conformers were calculated. This was narrowed to 22 with low energy being the criteria. It was the first helical cytokine receptor's structure to be determined in solution. The molecule has one polymer The structure reveals the nature of binding. A model of the IFNAR2 reveals a predominantly hydrophobic patch on the receptor that interacts with a matching hydrophobic surface on IFN-alpha. An adjacent motif of charged side chains then guides the proteins into a tight complex. The binding interface may account for crossreactivity and ligand specificity of the receptor. The source for experiments was human but was expressed in Escherichia coli.