Mode of action of heat-stable Escherichia coli enterotoxin. Tissue and subcellular specificities and role of cyclic GMP.
Some enteric strains of Escherichia coli release a heat-stable enterotoxin which, in contrast to cholera and heat-labile E. coli enterotoxins, stimulates guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2). We have examined the tissue spcificity of its action and the relation of its action to those of the 8-bromo analogues of cyclic GMP and cyclic AMP. Heat-stable enterotoxin stimulated guanylate cyclase activity and increased cyclic GMP concentration throughout the small and large intestine. It increased transepithelial electric potential difference and short-circuit current in the jejunum, ileum and caecum but not in the duodenum or distal colon. This pattern of electrical responses was mimicked by 8-bromo-cyclic GMP. However, 8-bromo-cyclic AMP produced an electrical response in all intestinal segments. The enterotoxin failed to stimulate guanylate cyclase inliver, lung, pancreas or gastric antral mucosa. In the intestines, it stimulated only the particulate and not the soluble form of the enzyme. Preincubation of the toxin with intestinal membranes did not render it capable of stimulating pancreatic guanylate cyclase. Cytosol factors did not enhance the toxin's stimulation of intestinal guanylate cyclase. This study supports the role of cyclic GMP as intracellular mediator for heat-stable enterotoxin and suggests that the toxin affects a membrane-mediated mechanism for guanylate cyclase activation that is unique to the intestines.
D000818:Animals; D002432:Cecum / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D003600:Cytosol / Q000502:physiology; D004386:Duodenum / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D005071:Evoked Potentials; D006162:Guanylate Cyclase / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects; D008297:Male; D008871:Microvilli / Q000187:drug effects; D011817:Rabbits
D004768:Enterotoxins; D006162:Guanylate Cyclase; D006152:Cyclic GMP