The binding of an extracellular ligand to a G protein-coupled receptor in the plasma membrane of a cell triggers intracellular signaling (Figure 1, A). After ligand binding, GTP replaces the GDP that is bound to Gsa, a subunit of the G protein (Figure 1, B). This causes Gsa to activate other cellular proteins, including adenylyl cyclase that converts ATP to cyclic AMP (cAMP). The cAMP activates protein kinases

(Figure 1, C). In cells that line the small intestine, a cAMP-activated protein kinase causes further signaling that ultimately results in the secretion of chloride ions (Cl−) from the cells. Under normal conditions, Gsa

hydrolyzes GTP to GDP, thus inactivating adenylyl cyclase and stopping the signal (Figure 1, A).

Figure 1. Under normal conditions, ligand binding to a G protein-coupled receptor results in chloride ion transport from an intestinal cell.

Individuals infected with the bacterium Vibrio cholerae experience severe loss of water from the body (dehydration). This is due to the effects of the bacterial cholera toxin that enters intestinal cells. Scientists studied the effects of cholera toxin on four samples of isolated intestinal cell membranes containing the

G protein-related signal transduction components shown in Figure 1. GTP was added to samples II and IV only; cholera toxin was added to samples III and IV only. The scientists then measured the amount of cAMP

produced by the adenylyl cyclase in each sample (Table 1).

TABLE 1. AMOUNT OF cAMP PRODUCED FROM INTESTINAL CELL MEMBRANES IN THE ABSENCE OR PRESENCE OF CHOLERA TOXIN

present, +; absent, −