These questions collapse into knowing which G-protein is coupled where.
Why this is true
There are only three G-protein outcomes to learn. Gs raises cyclic AMP, Gi lowers it, and Gq raises IP₃ and diacylglycerol, releasing intracellular calcium. The tissue then decides what that second messenger does: rising cAMP is stimulatory in the heart (β1) but relaxing in bronchial smooth muscle (β2), because smooth muscle protein kinase A phosphorylates and inactivates myosin light chain kinase. So the same messenger produces opposite mechanical effects in different tissues — which is precisely the trick most exam questions exploit.
Key points
- α1 → Gq → IP₃/DAG → vasoconstriction, mydriasis, bladder sphincter contraction.
- α2 → Gi → ↓cAMP → presynaptic inhibition, central sympatholysis (clonidine, dexmedetomidine).
- β1 → Gs → ↑cAMP → heart rate, contractility, renin release.
- β2 → Gs → bronchodilation, uterine relaxation, skeletal muscle vasodilation, potassium shift into cells.
- M2 → Gi (cardiac slowing); M1, M3 → Gq (secretions, gut motility, bronchoconstriction).
- D1 → Gs (renal vasodilation); D2 → Gi (antipsychotic target).
Pressor effects compared
| Drug | Receptors | Heart rate | Use |
|---|---|---|---|
| Phenylephrine | α1 | Reflex fall | Hypotension with tachycardia |
| Norepinephrine | α1 > β1 | Slight fall | Septic shock |
| Epinephrine | α and β | Rise | Anaphylaxis, cardiac arrest |
| Dobutamine | β1 | Rise | Cardiogenic shock |
| Isoproterenol | β1 = β2 | Marked rise | Bradycardia (rare now) |
Common traps
- Beta blockade in anaphylaxis makes adrenaline less effective — glucagon is the rescue because it bypasses the β receptor.
- Unopposed α stimulation after a non-selective beta blocker in cocaine toxicity worsens vasoconstriction.
MnemonicQiss and Qiq — α1, M1, M3 are Gq; α2, M2, D2 are Gi; the rest are Gs.
Test yourself
After an intravenous drug the mean arterial pressure rises and the heart rate falls, though the drug has no direct cardiac action.
High-yield
Reflex bradycardia after phenylephrine; no reflex change after a pure β1 agonist.