Lecture Notes: Types of Receptor Proteins

Overview of Receptor Proteins

• Four main types of receptor proteins.
• Importance of receptors in pharmacodynamics (study of how drugs interact with the body).
• Receptors mediate drug effects via specialized proteins on cell surfaces or within cells.

Role of Receptors

• Cellular communication: Recognize and respond to chemical messengers (e.g., neurotransmitters, hormones).
• Involved in functional changes in cells and organ systems.
• Key process: Signal transduction - steps occurring after a ligand binds to a receptor.
• Response times vary: Some receptors respond quickly (e.g., neurotransmission) while others have slower responses (e.g., steroid hormones).

Receptor Superfamilies

• Receptors can be classified into four main types:
  1. Ligand-gated ion channels (ionotropic receptors)
  2. G protein-coupled receptors (GPCRs)
  3. Kinase-linked receptors
  4. Nuclear receptors

1. Ligand-Gated Ion Channels

• Composed of transmembrane proteins forming a water-filled pore.
• Open or close based on ligand binding.
• Fastest response time (milliseconds).
• Examples: Nicotinic acetylcholine receptors, GABA type A receptors, glutamate receptors.
• Nicotinic acetylcholine receptors: Activated by acetylcholine; consist of five subunits; involved in fast neurotransmission.
• GABA receptors: Inhibitory neurotransmitter; drugs like diazepam enhance GABA effects.

2. G Protein-Coupled Receptors (GPCRs)

• Largest receptor superfamily.
• Structure: Single polypeptide chain crossing the membrane seven times.
• Divided into three classes (A, B, C).
• Ligand binding induces conformational change activating G proteins.
• Example: Beta-1 adrenergic receptor; activated by adrenaline, increases cyclic AMP levels leading to increased calcium influx in cardiac muscle cells, enhancing heart contraction.

3. Kinase-Linked Receptors

• Diverse receptor family activated by hormones, growth factors, cytokines.
• Composed of three domains: extracellular ligand binding, transmembrane, and intracellular kinase domain.
• Types:
  • Receptor tyrosine kinases (RTKs): e.g., epidermal growth factor receptor (EGFR); involved in cell growth.
  • Receptor serine/threonine kinases: Phosphorylate serine/threonine residues.
  • Cytokine receptors: Activate kinases upon ligand binding.
• EGFR Signaling: Ligand binding activates receptor, leading to cell proliferation and migration; significant in cancer treatment.

4. Nuclear Receptors

• Located mainly in the cytosol; translocate to the nucleus upon ligand binding.
• Function: Regulate gene transcription; affect metabolic and developmental processes.
• Classes:
  • Class I: Steroid receptors (e.g., glucocorticoids)
  • Class II: Thyroid hormone receptors
  • Class III: Homodimeric orphan receptors
  • Class IV: Monomeric orphan receptors
• Example: Aldosterone receptor; regulates sodium reabsorption in kidneys; drugs like spironolactone inhibit its effects, used for hypertension.

Summary of Response Times

• Ligand-gated ion channels: Fastest (milliseconds)
• GPCRs: Slightly slower (seconds)
• Kinase-linked receptors: Hours
• Nuclear receptors: Slowest (hours to days)

Conclusion

• Understanding different receptor types is crucial for comprehending cellular responses to ligands and drugs.
• Each receptor family has unique characteristics and mechanisms.