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Physiology · GI physiology: cholera toxin
Sample itemIn cholera the enterocyte secretes large volumes of chloride-rich fluid. Which sequence correctly describes the molecular action of the toxin?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. ADP-ribosylation of Gs protein, raising cAMP and opening the CFTR chloride channel
Vibrio cholerae toxin ADP-ribosylates the alpha subunit of the Gs protein so that adenylyl cyclase is permanently active. The resulting rise in cAMP activates protein kinase A, which opens CFTR chloride channels in the crypt cell apical membrane. Chloride, sodium and water are secreted into the lumen, causing rice-water stools.
Option by option
A. Cleavage of tight junction proteins, causing paracellular leak
Tight junction cleavage is not the main mechanism of cholera toxin; it acts through the cell's second messenger.
B. ADP-ribosylation of Gi protein, lowering cAMP and closing chloride channels
ADP-ribosylation of Gi is the action of pertussis toxin and it does not apply to cholera.
C. Inhibition of the sodium-potassium pump, causing cell swelling
Na/K pump inhibition is not the action of the toxin, and secretion is cAMP-driven.
D. ADP-ribosylation of Gs protein, raising cAMP and opening the CFTR chloride channel (correct)
Permanent Gs activation raises cAMP and opens CFTR.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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