The heat-stable toxin (STa) produced by enterotoxigenic E. coli causes secretory diarrhea through activation of which intracellular signaling pathway?

• A ADP-ribosylation of Gs protein increasing cAMP
• B Activation of phospholipase C generating IP3 and DAG
• C Inhibition of phosphodiesterase preserving cAMP
• D Activation of guanylate cyclase increasing cGMP ✓

Explanation

STa binds the membrane receptor guanylate cyclase C on enterocytes and directly stimulates its enzymatic activity, raising intracellular cyclic GMP. cGMP then activates protein kinase G and inhibits cAMP-dependent phosphodiesterase, resulting in net chloride secretion through CFTR channels with reduced sodium chloride absorption, producing watery diarrhea. ADP-ribosylation of Gs with raised cAMP is the mechanism of the heat-labile toxin LT and cholera toxin, which is the most tempting distractor here.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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