Pertussis toxin catalyzes ADP-ribosylation of Gi-alpha, rendering it permanently inactive. What would be the expected effect on cAMP levels in cells where Gi-coupled receptors are normally inhibitory?

• A cAMP levels would decrease markedly
• B cAMP levels would increase due to unopposed Gs stimulation ✓
• C cAMP levels would be unaffected as Gi has no role in adenylyl cyclase regulation
• D cAMP would be converted to cyclic GMP by phosphodiesterase

Explanation

Gi-alpha normally inhibits adenylyl cyclase when activated by inhibitory GPCR agonists (e.g., alpha-2 adrenergic, muscarinic M2, somatostatin receptors). Pertussis toxin ADP-ribosylates the cysteine residue near the C-terminus of Gi-alpha, preventing receptor-Gi coupling. Without Gi-mediated inhibition, adenylyl cyclase activity (driven by Gs) proceeds unopposed, causing elevated intracellular cAMP. This is the molecular basis of pertussis toxin's effect in promoting lymphocytosis and blocking immune cell chemotaxis. Cholera toxin (not pertussis) locks Gs-alpha in the active state.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.