beta-2 adrenergic receptor binding

Definition

Target type: molecularfunction

Binding to a beta-2 adrenergic receptor. [GOC:mah, GOC:nln]

Beta-2 adrenergic receptor binding involves the interaction of epinephrine (adrenaline) or norepinephrine (noradrenaline) with the beta-2 adrenergic receptor (β2AR), a G protein-coupled receptor (GPCR) located on the cell membrane. This binding initiates a signaling cascade that ultimately leads to various physiological effects, including bronchodilation, vasodilation, and glycogenolysis. Here's a detailed breakdown of the molecular function:

1. **Ligand Binding:** Epinephrine or norepinephrine, acting as ligands, bind to the extracellular domain of the β2AR. This binding event induces a conformational change in the receptor, activating it.
2. **G Protein Coupling:** The activated β2AR interacts with a heterotrimeric G protein, specifically the Gs protein. This interaction causes the G protein to dissociate, releasing its α subunit, which is bound to GTP.
3. **Adenylate Cyclase Activation:** The activated α subunit of Gs protein binds to and activates adenylate cyclase, an enzyme responsible for converting ATP into cyclic AMP (cAMP).
4. **cAMP Production:** Adenylate cyclase catalyzes the production of cAMP, acting as a second messenger.
5. **Protein Kinase A Activation:** cAMP binds to and activates protein kinase A (PKA), a key enzyme in the signaling cascade.
6. **Downstream Signaling:** Activated PKA phosphorylates various downstream proteins, leading to a variety of cellular responses. These responses include:
- **Bronchodilation:** Relaxation of smooth muscle in the bronchioles, facilitating airflow.
- **Vasodilation:** Relaxation of smooth muscle in blood vessels, promoting blood flow.
- **Glycogenolysis:** Breakdown of glycogen into glucose in the liver and muscles, increasing blood glucose levels.
- **Increased Heart Rate and Contractility:** Stimulation of heart muscle cells, leading to an increased heart rate and force of contraction.
7. **Desensitization:** Following prolonged exposure to ligands, the β2AR undergoes desensitization, a process that reduces receptor sensitivity and signaling. This involves phosphorylation of the receptor by G protein-coupled receptor kinases (GRKs) and binding of β-arrestin proteins, which inhibit further signal transduction.

The β2AR binding and subsequent signaling cascade is tightly regulated, ensuring appropriate responses to physiological demands. Dysregulation of this pathway can contribute to various diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cardiovascular disorders.'
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Proteins (4)

Compounds (150)