G Protein-Coupled Receptors (GPCRs)

G protein-coupled receptors (GPCRs), also called G protein-linked receptors (GPLRs), are a large family of receptors found on cell membranes. GPCRs are receptors that a.) are activated by circulating molecules (ie, neurotransmitters or hormones) and that b.) trigger signaling cascades (“signal transduction pathways” or “second messenger systems”) to create cellular responses. These receptors are coupled to G proteins, which do the actual triggering of different signaling cascades.

There are two main signaling pathways ("second messenger systems") that are affected by GPCRs:

1. the cAMP signaling pathway, and
2. the phosphatidylinositol signaling pathway

There are three main GPCR subtypes that either stimulate or inhibit these signaling pathways:

1. Gq (when activated, stimulates the phosphatidylinositol signaling pathway),
2. Gs (when activated, stimulates the cAMP signaling pathway), and
3. Gi (when activated, inhibits the cAMP signaling pathway).

If a receptor is coupled to a Gq protein, the receptor will activate the phosphatidylinositol signaling pathway in the cell.

Examples of receptors that activate Gq protein signaling include:

• M1 muscarinic receptors (activated by acetylcholine) in the central nervous system
• M3 muscarinic receptors (activated by acetylcholine) in smooth muscle
• alpha-1 adrenergic receptors (activated by norepinephrine) in smooth muscle/blood vessels

If a receptor is coupled to a Gs protein, the receptor will activate the cAMP signaling pathway in the cell.

Examples of receptors that activate Gs protein signaling include:

• beta-1 adrenergic receptors (activated by norepinephrine) in the heart (cardiac nodal cells and ventricular myocytes)
• beta-2 adrenergic receptors (activated by norepinephrine) in smooth muscle

If a receptor is coupled to a Gi protein, the receptor will inhibit the cAMP signaling pathway in the cell.

Examples of receptors that activate Gi protein signaling include:

• M2 muscarinic receptors (activated by acetylcholine) in the heart (cardiac nodal cells and atrial myocytes)
• alpha-1 adrenergic receptors in smooth muscle