U01.05.016 G-protein–linked second messengers

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Learning Objective

By the end of this section, you should be able to associate major receptor families with their corresponding G-protein classes (Gq, Gi, Gs) and predict the downstream physiologic effects—a high-yield framework for USMLE Step 1 pharmacology and physiology questions.

G-Protein–Linked Second Messengers

Many clinically important receptors signal through G-proteins, which activate intracellular second-messenger pathways. Remember:

Gq → ↑ IP₃/DAG → ↑ intracellular Ca²⁺
Gi → ↓ cAMP
Gs → ↑ cAMP

Adrenergic Receptors

Receptor	G-protein	Major functions
α₁	Gq	Vascular smooth muscle contraction (vasoconstriction), pupillary dilator muscle contraction (mydriasis), and intestinal and bladder sphincter contraction
α₂	Gi	↓ Sympathetic outflow, ↓ insulin release, ↓ lipolysis, ↑ platelet aggregation, ↓ aqueous humor production
β₁	Gs	↑ Heart rate, ↑ contractility (one heart), ↑ renin release, ↑ lipolysis
β₂	Gs	Vasodilation, bronchodilation (two lungs), ↑ lipolysis, ↑ insulin release, ↑ glycogenolysis, ↓ uterine tone (tocolysis), ↑ aqueous humor production, ↑ cellular K⁺ uptake
β₃	Gs	↑ Lipolysis, ↑ thermogenesis in skeletal muscle, and bladder relaxation

Cholinergic (Muscarinic) Receptors

Receptor	G-protein	Major functions
M1	Gq	Higher cognitive function, stimulation of the enteric nervous system, ↑ and exocrine gland secretion
M2	Gi	↓ Heart rate, ↓ AV node conduction velocity, ↓ atrial contractility
M3	Gq	↑ Exocrine gland secretion, ↑ gut peristalsis, bladder contraction, bronchoconstriction, vasodilation (via NO), pupillary sphincter contraction (miosis), ciliary muscle contraction (accommodation)

Dopamine Receptors

Receptor	G-protein	Major functions
D1	Gs	Renal vasodilation (relaxes renal vascular smooth muscle), activates the direct pathway in the striatum
D2	Gi	Inhibits neurotransmitter release in the brain, inhibits the indirect pathway of the striatum

Histamine Receptors

Receptor	G-protein	Major functions
H1	Gq	Bronchoconstriction, ↑ mucus production, ↑ vascular permeability, vasodilation, and pruritus
H2	Gs	↑ Gastric acid secretion

Vasopressin (ADH) Receptors

Receptor	G-protein	Major functions
V1	Gq	Vascular smooth muscle contraction (vasoconstriction)
V2	Gs	↑ Water permeability and reabsorption in collecting tubules via aquaporin-2 insertion, ↑ release of von Willebrand factor