From Escherichia coli heat-stable enterotoxin to mammalian endogenous guanylin hormones

A.A.M Lima,M.C Fonteles

doi:10.1590/1414-431x20133063

Abstract

The isolation of heat-stable enterotoxin (STa) from Escherichia coli and cholera toxin from Vibrio cholerae has increased our knowledge of specific mechanisms of action that could be used as pharmacological tools to understand the guanylyl cyclase-C and the adenylyl cyclase enzymatic systems. These discoveries have also been instrumental in increasing our understanding of the basic mechanisms that control the electrolyte and water balance in the gut, kidney, and urinary tracts under normal conditions and in disease. Herein, we review the evolution of genes of the guanylin family and STa genes from bacteria to fish and mammals. We also describe new developments and perspectives regarding these novel bacterial compounds and peptide hormones that act in electrolyte and water balance. The available data point toward new therapeutic perspectives for pathological features such as functional gastrointestinal disorders associated with constipation, colorectal cancer, cystic fibrosis, asthma, hypertension, gastrointestinal barrier function damage associated with enteropathy, enteric infection, malnutrition, satiety, food preferences, obesity, metabolic syndrome, and effects on behavior and brain disorders such as attention deficit, hyperactivity disorder, and schizophrenia.

Highlights

The heat-stable enterotoxin (Sta) from Escherichia coli is the main agent promoting traveler’s diarrhea and is one of the main enterotoxins responsible for diarrhea, dehydration, and death during the first two years of life in many parts of the developing world [1]
Over the last four decades, research on bacterial toxins including cholera toxin from V. cholerae and stable enterotoxin (STa) enterotoxin from E. coli has been instrumental in increasing our understanding of the importance of electrolyte and water balance in normal intestine and kidney function [20,21,59]
An independent study by Currie et al [6] published almost at the same time reported an endogenous activator of intestinal GC that had a peptide structure similar to that of the STa enterotoxin; they named this molecule as guanylin

Summary

Introduction

The heat-stable enterotoxin (Sta) from Escherichia coli is the main agent promoting traveler’s diarrhea and is one of the main enterotoxins responsible for diarrhea, dehydration, and death during the first two years of life in many parts of the developing world [1]. GC-C is conserved evolutionarily in several species, including fish, teleost, birds, and mammals [48], and this is consistent with the functional activities associated with STa peptides and related hormones, as described in the present report.

Results

Conclusion