Distribution of Escherichia coli heat-stable enterotoxin/guanylin/uroguanylin receptors in the avian intestinal tract.
Pathogenic strains of enteric bacteria secrete small heat-stable toxins (STs) that activate membrane guanylyl cyclase receptors found in the intestine. The intestinal peptide agonists, guanylin and uroguanylin, are structurally related to STs. Receptors for 125I-ST were found throughout the entire length of the intestinal tract of all the birds examined. These receptors were restricted to intestinal epithelial cells covering villi and forming intestinal glands and were not observed in other strata of the gut wall. The most intense labeling of receptors by 125I-ST occurred in the region of the microvillus border of individual enterocytes. There appeared to be a decrease in receptor density distally along the length of the small intestine, although labeling of receptors by 125I-ST was observed throughout the small intestine and colon. Cellular cGMP accumulation responses to Escherichia coli ST and rat guanylin in the domestic turkey and duck were greater in the proximal small intestine compared to the distal small intestine or colon. Brush border membranes (BBM) isolated from the mucosa of proximal small intestine of turkeys exhibited agonist-stimulated guanylyl cyclase activity. The rank order potency for enzyme activation was E. coli ST > uroguanylin > guanylin. Competitive radioligand binding assays using 125I-ST and turkey intestine BBM revealed a similar rank order affinity for the receptors that was exemplified by the Kd values of ST 2.5 nM, uroguanylin 80 nM and guanylin 2.6 microM. It may be concluded that functional receptors for the endogenous peptides, guanylin and uroguanylin, occur in the apical membranes of enterocytes throughout the avian intestine. The receptor-guanylyl cyclase(s) of proximal small intestine were preferentially activated by uroguanylin relative to guanylin, but both endogenous peptides were less potent than their molecular mimic, E. coli ST.
Krause
W J
WJ
Department of Pathology and Anatomical Sciences, University of Missouri, Columbia 65212, USA.
Freeman
R H
RH
Eber
S L
SL
Hamra
F K
FK
Fok
K F
KF
Currie
M G
MG
Forte
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001681:Biological Assay; D001717:Birds / Q000378:metabolism*; D004355:Drug Stability; D004768:Enterotoxins / Q000737:chemistry; D004926:Escherichia coli; D005768:Gastrointestinal Hormones; D006162:Guanylate Cyclase / Q000378:metabolism*; D006358:Hot Temperature; D007413:Intestinal Mucosa / Q000378:metabolism*; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D014018:Tissue Distribution
D004768:Enterotoxins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D018000:Receptors, Peptide; C072685:guanylin; C084362:uroguanylin; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled