E. coli heat-stable enterotoxin and guanylyl cyclase C: new functions and unsuspected actions.
Some E. coli cause diarrhea by elaborating heat-labile and heat-stable (ST) enterotoxins which stimulate intestinal secretion. E. coli ST's are small peptides which bind to intestinal luminal epithelial cell receptors. The ST receptor, one of a family of receptor-cyclases called guanylyl cyclase C (GC-C), is a membrane spanning protein containing an extracellular binding domain and intracellular protein kinase and catalytic domains. The intestine synthesizes and secretes homologous peptides, guanylin and uroguanylin. The kidney also synthesizes uroguanylin. ST, guanylin or uroguanylin binding to GC-C results in increased cGMP, phosphorylation of the CFTR Cl- channel and secretion. Proguanylin and prouroguanylin circulate in blood and bind to receptors in intestine, kidney, liver, brain etc. In the kidney, they stimulate the excretion of Na+ and K+. Study of GC-C "knock-out" mice reveal that GC-C is important to intestinal salt and water secretion, duodenal bicarbonate secretion, recovery from CCl4-induced liver injury, and to intestinal polyp formation in Min mice lacking GC-C.
Giannella
Ralph A
RA
Division of Digestive Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0595, USA. ralph.giannella@uc.edu
Mann
Elizabeth A
EA
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D003967:Diarrhea / Q000209:etiology / Q000503:physiopathology; D004768:Enterotoxins / Q000235:genetics / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000209:etiology / Q000503:physiopathology; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones / Q000502:physiology; D006162:Guanylate Cyclase / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007417:Intestinal Polyps / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides; D010455:Peptides / Q000502:physiology; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); C072685:guanylin; C084362:uroguanylin; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled