G Protein-Coupled Receptors: Gq, Gs and Gi Explained
How do G protein-coupled receptors signal through Gq, Gs and Gi?
G protein-coupled receptors receive a signal outside the cell and activate a G protein inside it. Gq usually activates phospholipase C and releases stored calcium through IP3. Gs stimulates adenylyl cyclase and increases cyclic AMP. Gi inhibits adenylyl cyclase, while its beta-gamma subunits also regulate ion channels. The proteins in the target tissue determine the final response.
Key takeaways
- Gq, Gs and Gi describe G-protein alpha-subunit families, rather than three separate drug classes.
- Beta-1 and beta-2 both use Gs, but the heart and airway respond differently because their target proteins differ.
- Milrinone raises cyclic AMP by slowing its breakdown through PDE3 inhibition.
In this video
- Why do 3 different drugs share 1 receptor family?
- What is a receptor?
- What are the 4 major receptor families?
- How does a G protein-coupled receptor work?
- What does the G protein do?
- What do Gq-coupled, Gs-coupled, and Gi-coupled mean?
- What is a second messenger?
- How does the Gq pathway work?
- Does calcium always mean contraction?
- Which bedside drugs use the Gq pathway?
- How does the Gs pathway work?
- How does beta-1 make the heart contract harder?
- How does albuterol relax the airway through beta-2?
- Why does epinephrine act differently in each tissue?
- How does milrinone raise cyclic AMP?
- How are Gq and Gs different?
- How does the Gi pathway work?
- What does Gi do in the heart and brain?
- Why does Precedex cause bradycardia and a low MAP?
- How do you explain a drug in a CRNA school interview?
- How do Gq, Gs, and Gi compare?
How does a G protein-coupled receptor pass a signal?
A ligand, such as a drug or neurotransmitter, binds a receptor in the cell membrane. The receptor helps the G protein exchange GDP for GTP on its alpha subunit. Activated alpha and beta-gamma components then regulate enzymes or ion channels inside the cell.
Second messengers carry and amplify this signal. Cyclic AMP, IP3, DAG and calcium have different jobs, so memorizing the pathway name alone does not explain what happens to the patient. Follow the receptor, intracellular signal and tissue response in order.
Why do Gq and Gs produce different effects in different tissues?
Phenylephrine activates alpha-1 receptors on vascular smooth muscle. Gq activates phospholipase C, IP3 releases calcium, and calcium-calmodulin activates myosin light-chain kinase. The vessel contracts and vascular resistance rises.
Beta-1 signaling in cardiac muscle uses Gs, cyclic AMP and protein kinase A to support calcium handling and stronger contraction. Beta-2 signaling uses the same relay in airway smooth muscle, where protein kinase A reduces contraction and supports bronchodilation. Calcium and cyclic AMP are signals. Their effect depends on the proteins receiving them.
How does Gi connect to Precedex and a slower heart rate?
Dexmedetomidine activates alpha-2 receptors and reduces sympathetic signaling. Gi inhibits adenylyl cyclase. Beta-gamma signaling also inhibits calcium entry at nerve endings and regulates potassium channels, reducing neurotransmitter release and excitability. Bradycardia and hypotension follow from the drug’s effects on sympathetic activity.
For interview practice, explain one drug all the way from receptor to bedside effect. Include the tradeoff: raising vascular tone also raises afterload, and a higher arterial pressure does not by itself prove cardiac output improved.
