Learning Objective

Understand the basic principle that drug-receptor binding activates specific signaling mechanisms and recognize the major types of drug-responsive signaling pathways.

When an agonist binds to its receptor, it activates an effector system that converts the binding event into a cellular response. Different receptors use different intracellular signaling pathways. Major Types of Signaling Mechanisms:

Ligand-gated ion channels

• Rapid response (milliseconds).
• Agonist binding opens an ion channel → changes membrane potential.
• Example: Nicotinic acetylcholine receptor (Na⁺ influx → depolarization).

G protein-coupled receptors (GPCRs)

• Slower response (seconds).
• Agonist binding activates G proteins, which modulate second messengers such as cAMP, IP3, DAG, or Ca²⁺.
• Examples: β-adrenergic receptor, muscarinic acetylcholine receptor.

Enzyme-linked receptors

• Usually, receptor tyrosine kinases.
• Agonist binding activates intrinsic kinase activity → phosphorylates target proteins.
• Example: Insulin receptor.

Intracellular (nuclear) receptors

• Slow response (hours).
• Lipophilic agonists (e.g., steroid hormones) diffuse into the cell → bind receptors → alter gene transcription.
• Example: Glucocorticoid receptor, Tetesterone

Activity