Choleratoxin

• UniProt: P01555

• UniProt: P01556

The cholera toxin ( CTX ) is a Vibrio cholerae and eltor produced by the bacteria Vibrio exotoxin, which can cause severe diarrheal disease in humans. The enterotoxin is the trigger of cholera.

Mechanism of action

The cholera toxin is a hexameric protein composed of an α - and β - five subunits. It passes through the plasma membrane and inhibits GTPase activity of Gαs - subunit of a heterotrimeric G protein by this ADP- ribosylated ( from intracellular NAD). Thereby the intrinsic GTPase activity of the Gαs - subunit which converts GTP to GDP, blocked - the G protein remains in the active state. It activates permanently the adenylate cyclase, there is an excess of the second messenger cAMP. So that the activity of specific membrane channels is changed.

Pathophysiological effects on the intestinal epithelium

The permanently increased cAMP leads to increased incorporation of the chloride channel, cystic fibrosis transmembrane conductance regulator ( CFTR) into the membrane and thereby to an increased loss of Cl - ions in the lumen. In addition, there is a Na loss by inhibition of the Na / H exchanger ( NHE3 ) and the Na channel ( Epithelial sodium channel, ENaC), which is responsible for the Na reabsorption in the epithelium. In addition, it is believed that the tight junctions permeability increases between the epithelial cells. As a result, dehydration and electrolyte depletion resulting from loss of NaCl and removal of H2O from the epithelium, which follows the NaCl passively into the intestinal lumen. It can lead to severe diarrhea, with loss of water up to one liter per hour, also be massive efflux of potassium and bicarbonate ions from the gut

Overall, this leads to the symptoms of cholera.