G protein-coupled receptors

Definition

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in cellular communication by responding to various external signals. When activated by ligands such as hormones, neurotransmitters, or other signaling molecules, GPCRs undergo a conformational change that allows them to interact with G proteins, which then trigger downstream signaling pathways within the cell. This mechanism is essential for various physiological processes, including sensory perception, immune responses, and neurotransmission.

5 Must Know Facts For Your Next Test

1. GPCRs are the largest family of membrane proteins in the human genome, with over 800 different types identified.
2. They are involved in a wide range of biological functions, making them key targets for pharmaceutical drugs; approximately 30-40% of all modern medicinal drugs act on GPCRs.
3. Upon ligand binding, GPCRs activate G proteins by promoting the exchange of GDP for GTP on the G protein's alpha subunit.
4. The signaling pathways activated by GPCRs can lead to various cellular responses, including changes in gene expression, enzyme activity, and ion channel conductance.
5. GPCR desensitization is a process where prolonged exposure to a ligand leads to a decrease in receptor activity, preventing overstimulation of the cell.

Review Questions

• How do G protein-coupled receptors initiate signaling cascades upon activation?
  • When a ligand binds to a GPCR, it causes the receptor to undergo a conformational change. This change allows the GPCR to interact with an associated G protein, leading to the exchange of GDP for GTP on the G protein's alpha subunit. Once activated, the G protein can dissociate into its subunits and interact with various downstream effectors, such as enzymes or ion channels, initiating signaling cascades that result in specific cellular responses.
• Discuss the role of G protein-coupled receptors in drug development and their significance in pharmacology.
  • GPCRs are crucial targets in drug development because they regulate numerous physiological processes and are implicated in many diseases. Approximately 30-40% of all modern pharmaceuticals target GPCRs, making them one of the most important classes of drug targets. Understanding the mechanisms of GPCR activation and signaling has led to the development of selective agonists and antagonists that can modulate these pathways effectively, offering therapeutic benefits for conditions such as hypertension, depression, and cancer.
• Evaluate the impact of GPCR desensitization on cellular responsiveness and its implications for therapeutic interventions.
  • GPCR desensitization occurs when continuous stimulation by a ligand leads to reduced receptor activity, often through phosphorylation or internalization of the receptor. This process can significantly affect cellular responsiveness and adaptation to prolonged exposure to stimuli. For therapeutic interventions, understanding desensitization is vital; it can inform strategies to improve drug efficacy or minimize side effects by timing drug administration or using combination therapies that avoid rapid receptor desensitization.

Related terms

Ligand: A molecule that binds to a receptor and initiates a cellular response.

G Protein: A molecular switch that transmits signals from activated receptors to target proteins inside the cell.

Second Messenger: Intracellular signaling molecules that relay signals received by cell surface receptors to target molecules within the cell.