Upregulation of Escherichia coli heat-stable enterotoxin receptor in regenerating rat liver.
Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin and for Escherichia coli heat-stable toxin (STa). Binding of either guanylin or STa to intestinal GC-C results in net chloride secretion. Although GC-C is expressed in the rat intestine throughout life, its expression in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this receptor in the liver, we tested the hypothesis that GC-C mRNA expression could be induced in the adult rat liver following 1) partial hepatectomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carbon tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injection, which generates an acute phase response without hepatocyte proliferation. We demonstrated expression of GC-C mRNA in the regenerating rat liver following either partial hepatectomy or CCl4-induced hepatic necrosis. We have also shown that GC-C mRNA expression occurred in association with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to liver plasma membranes prepared from turpentine-treated rats. Maximal expression of GC-C occurred in preparations enriched for the canalicular domain. Although the function of GC-C in the liver is unknown, localization to the canalicular domain would be consistent with a role for GC-C in hepatic chloride secretion, especially in the perinatal liver and during hepatocyte regeneration.
Laney
D W
DW
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati 45229.
Bezerra
J A
JA
Kosiba
J L
JL
Degen
S J
SJ
Cohen
M B
MB
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D015139:Blotting, Southern; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D015342:DNA Probes; D004768:Enterotoxins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000378:metabolism; D006498:Hepatectomy; D007082:Ileum / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D045265:Natriuretic Peptides; D015345:Oligonucleotide Probes; D010455:Peptides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D014425:Turpentine / Q000633:toxicity; D015854:Up-Regulation
D001427:Bacterial Toxins; D015342:DNA Probes; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D015345:Oligonucleotide Probes; D010455:Peptides; D012333:RNA, Messenger; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); C072685:guanylin; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D014425:Turpentine