SYSTEM
MECHANISM
EXAMPLES
CLUE · DRUG
3 Na⁺ out, 2 K⁺ in, 1 ATP; phosphorylated on the cytosolic side
All cells; drives secondary transport
Digoxin, ouabain bind the K⁺ site → inhibit
Adenylyl cyclase ↑ → cAMP → protein kinase A
β₁, β₂, D₁, H₂, V₂ receptors; glucagon, PTH, TSH, ACTH, LH/FSH, calcitonin, CRH, GHRH
Cholera toxin locks Gs on
Adenylyl cyclase ↓ → ↓ cAMP
α₂, M₂, D₂, opioid receptors, GABA-B
Pertussis toxin blocks Gi (↑ cAMP)
Phospholipase C → IP₃ (↑ Ca²⁺ from ER) + DAG (PKC)
α₁, M₁, M₃, H₁, V₁; GnRH, TRH, oxytocin, angiotensin II, gastrin
H₁, α₁, V₁, M₁, M₃ receptors
Guanylyl cyclase → cGMP → PKG → smooth muscle relaxation
ANP/BNP (receptor GC), nitric oxide (soluble GC)
Nitrates, sildenafil (blocks PDE5 breakdown)
Ligand → dimerization → autophosphorylation → RAS–MAPK, PI3K–Akt
Insulin, IGF-1, EGF, PDGF, FGF, VEGF
Imatinib, erlotinib, trastuzumab (HER2)
JAK-STAT (non-receptor TK)
Receptor-associated JAK phosphorylates STAT → nucleus
Cytokines (IL-2, IL-6, interferons), GH, prolactin, EPO, G-CSF, thrombopoietin
JAK2 V617F (polycythemia vera) · tofacitinib, ruxolitinib
Lipophilic hormones cross the membrane → zinc-finger receptor → DNA response element
Cortisol, aldosterone, sex steroids, T₃/T₄, vitamin D, retinoic acid
Slow onset, long-lasting effects
Ligand-gated ion channels
Neurotransmitter opens a channel directly (fast)
Nicotinic ACh, GABA-A, NMDA, 5-HT₃
Benzodiazepines, neuromuscular blockers, ondansetron
Phospholipid bilayer with cholesterol (↓ fluidity, ↑ stiffness), sphingolipids and glycolipids
Myelin rich in sphingomyelin
Spur cells from excess membrane cholesterol (liver disease)