Cholera toxin can affect cells by inhibiting the ability of the G protein α subunit to hydrolyze GTP to GDP. On a cellular level, which one of the following would be helpful in reducing the harmful effect of cholera toxin?
a. Increasing the amount of intracellular cAMP.
b. Inhibiting the activity of adenylyl cyclase in the cell.
c. Adding ligand for the G-protein coupled receptor in this
pathway.
d. Increasing the amount of protein kinase A activity in the
cell.
e. Inhibiting the activities of the β and γ G-protein subunits.

b. Inhibiting the activity of adenylyl cyclase in the cell.

Explanation:

Cholera toxin enters the interstitial epithelial cells with the help of 5 identical B sub units and 1 A sub unit. A sub unit is catalytic and it is endocytosed in  interstitial epithelial cells.  Inside cells, A sub unit is cleaved into two fragments A1 and A2 with the help of proteases. A1 upon interaction with a small cytosolic G protein named as ARF-6 activates Gsα protein permanently by post translation modification known as ribosylation. This Gsα protein further acts upon an intracellular adenylate cyclase. The adenylate cyclase constitutively produces cyclic AMP (cAMP) which acts upon CFTR chloride ion channel and Na⁺ and H⁺ exchanger. As a result of this, large efflux of NaCl occurs. After NaCl loss, inside condition becomes hypotonic which leads to loss of water from the cells. This condition causes diarrhea .

But if activity of adenylate cyclase can be inhibited, the signaling cascade will come to an end leading to reduced harmful effect of cholera toxin.

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