Escherichia coli heat-stable enterotoxins, guanylins, and their receptors: what are they and what do they do?
STa represents a family of homologous heat-stable peptide toxins that are elaborated by a variety of bacteria capable of causing enteric disease in human beings. All these peptides have a tertiary structure, maintained by disulfide bridges, which is required for receptor occupancy and biologic activity. The toxins have highly homologous carboxy-terminal domains and variable differences at the amino-terminal domain. The amino-terminal domain of these various peptides is not required for biologic activity. Recently an endogenous ligand called guanylin has been extracted from mammalian intestine and shown to bind the STa receptor. A similar peptide, called uroguanylin, has been found in human and animal urine. It is likely that guanylin and uroguanylin are indeed endogenous ligands for the STa receptor and may be modulators of Cl- secretion in the intestine, kidney, and perhaps in other organs. The STa-guanylin receptors are located on enterocytes, colonocytes, and various extraintestinal tissues. These receptors are one of a family of transmembrane guanylate cyclases that have homologous intracytoplasmic domains but divergent extracellular domains. It is likely that the extracellular domains of these various receptor cyclases confer specificity for ligand binding. Although GC-C, the STa receptor, may also be a receptor for guanylin, other receptors may exist that may be more specific for guanylin.(ABSTRACT TRUNCATED AT 250 WORDS)
Giannella
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Division of Digestive Diseases, University of Cincinnati College of Medicine, OH 45267-0595.
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides; D010455:Peptides / Q000737:chemistry / Q000502:physiology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; C034151:heat stable toxin (E coli); C072685:guanylin; D006162:Guanylate Cyclase