Learning Objective
By the end of this note, the learner should be able to: Differentiate between Gs, Gi, and Gq-coupled receptor signaling pathways and identify key ANS receptors associated with each pathway.
Many membrane receptors signal through G-proteins, which regulate intracellular enzymes and second messengers. These receptors typically have 7 transmembrane domains (“serpentine receptors”).
Gs Pathway – Stimulatory
Function: ↑ cAMP by stimulating adenylyl cyclase → activates protein kinase A (PKA) → phosphorylation of enzymes & transcription factors (e.g., CREB).
Receptors using Gs:
- β1, β2 adrenergic
- D1 dopamine
- H2 histamine
- Glucagon
- Prostacyclin (PGI₂)
- Some serotonin receptors
Gi Pathway – Inhibitory
Function: ↓ cAMP by inhibiting adenylyl cyclase.
Receptors using Gi:
- α2 adrenergic
- M2 muscarinic
- D2 dopamine
- Several opioid receptors
- Some serotonin receptors
Gq Pathway – Ca²⁺ / IP₃ / DAG
Function: Activation of phospholipase C (PLC) →
- PIP₂ → IP₃ + DAG
- IP₃ → ↑ Ca²⁺ release from SR
- DAG + Ca²⁺ → activates protein kinase C (PKC)
Receptors using Gq:
- α1 adrenergic
- M1, M3 muscarinic
- Angiotensin II
- Several serotonin receptors
Quick ANS Table (High-Yield)
| Pathway | Receptors | Effect |
|---|---|---|
| Gs | β1, β2, D1 | ↑ cAMP |
| Gi | M2, α2, D2 | ↓ cAMP |
| Gq | M1, M3, α1 | IP₃/DAG → ↑ Ca²⁺ |
Clinical Correlate – NO Pathway
Some drugs act via nitric oxide, which activates guanylyl cyclase → ↑ cGMP.
Drugs:
- Nitrates (nitroglycerin)
- M-receptor agonists (bethanechol)
Endogenous mediators:
- Bradykinin, histamine
