G protein-coupled receptors

Definition

G protein-coupled receptors (GPCRs) are a large family of membrane proteins that play a crucial role in transmitting signals from outside the cell to the inside. They detect molecules outside the cell, such as hormones and neurotransmitters, and activate internal signaling pathways through the associated G proteins, influencing various physiological processes. GPCRs are involved in many cellular responses, including sensory perception, immune responses, and cell growth.

5 Must Know Facts For Your Next Test

1. GPCRs are involved in approximately 80% of all modern medicinal drugs, highlighting their importance in pharmacology.
2. They can activate multiple signaling pathways, leading to diverse effects within the same cell or tissue.
3. There are over 800 different types of GPCRs in humans, each responding to specific ligands and serving unique functions.
4. The activation of GPCRs can lead to changes in intracellular calcium levels, activation of kinases, and alterations in gene expression.
5. Mutations or dysregulation of GPCRs are linked to various diseases, including cancer, cardiovascular diseases, and mental health disorders.

Review Questions

• How do G protein-coupled receptors initiate intracellular signaling pathways upon activation?
  • When a ligand binds to a GPCR on the cell surface, it causes a conformational change in the receptor. This change activates the associated G protein by exchanging GDP for GTP. The activated G protein then dissociates and interacts with other proteins or enzymes inside the cell, initiating various signaling cascades that lead to cellular responses.
• Discuss the role of second messengers in the signaling pathways activated by G protein-coupled receptors.
  • Second messengers are critical components of the signaling pathways initiated by GPCRs. Upon activation of a GPCR, the associated G proteins can stimulate or inhibit enzymes that produce second messengers like cyclic AMP (cAMP) or inositol trisphosphate (IP3). These second messengers amplify the signal within the cell by activating protein kinases or opening ion channels, leading to a rapid and diverse range of cellular responses.
• Evaluate the significance of desensitization in the context of G protein-coupled receptors and its implications for drug development.
  • Desensitization of G protein-coupled receptors is a vital regulatory mechanism that prevents overstimulation in response to prolonged exposure to agonists. This process can involve receptor phosphorylation and internalization, leading to reduced sensitivity to future stimulation. Understanding desensitization is crucial for drug development because it can influence therapeutic efficacy and tolerance. Targeting this mechanism can help design drugs that maintain receptor responsiveness while minimizing side effects associated with chronic use.

Related terms

G proteins: G proteins are molecular switches that transmit signals from activated GPCRs to downstream effectors, playing a key role in various signaling pathways.

Second messengers: Second messengers are small molecules that relay signals received by GPCRs to target molecules within the cell, amplifying the signal and eliciting a cellular response.

Desensitization: Desensitization is a process where prolonged exposure to an agonist reduces the receptor's responsiveness, often involving phosphorylation and internalization of GPCRs.