Lesson 3

Overview of G Protein-Coupled Receptors (GPCRs)

  • GPCR signaling sequence: First Messenger (Ligand) → GPCR → Effector → Second Messenger → Cellular response.

G Protein Structure

  • Composed of three subunits: alpha, beta, and gamma.

G Protein Activation

  • Ligand binding activates the G protein, influencing the effector's activity (turns on/off).

Role of Effectors

  • Effectors activate or inhibit second messengers, leading to specific cellular responses.

Second Messengers

  • Key second messengers include:
    1. Cyclic adenosine monophosphate (cAMP)
    2. Cyclic guanosine monophosphate (cGMP)
    3. Inositol triphosphate (IP3)
    4. Diacylglycerol (DAG)
    5. Calcium ion (Ca+2)

Tissue-Specific Responses

  • Second messengers lead to unique intracellular reactions depending on the cell type, affecting various physiological processes (e.g., epinephrine effects on cardiac vs. bronchial muscles).

Summary of Steps in GPCR Signaling

  1. First Messenger: Ligand binds to GPCR (can be endogenous or exogenous).
  2. G Protein Function: Alpha subunit dissociates and alters effector activity, depending on whether it is stimulatory (Gs, Gq) or inhibitory (Gi).
  3. Effector Activation: Produces or activates second messengers through enzymes or ion channels.
  4. Signal Amplification: Second messengers increase response magnitude by initiating a cascade of physiological changes.
  5. Cellular Response: Specific actions through modulated enzymatic networks (kinases, phosphatases) tailored to cell type.