Receptors and cGMP signalling mechanism for E. coli enterotoxin in opossum kidney.
Receptors for the heat-stable enterotoxin produced by Escherichia coli were found in the kidney and intestine of the North American opossum and in cultured renal cell lines. The enterotoxin markedly increased guanosine 3',5'-cyclic monophosphate (cGMP) production in slices of kidney cortex and medulla, in suspensions of intestinal mucosa, and in the opossum kidney (OK) and rat kangaroo kidney (PtK-2) cell lines. In contrast, atrial natriuretic factor elicited much smaller increases in cGMP levels of kidney, intestine, or cultured kidney cell lines. The enterotoxin receptors in OK cells had a molecular mass of approximately 120 kDa when measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of receptors crosslinked with 125I-enterotoxin. The occurrence of receptors for the E. coli peptide in OK implies that these receptors may be involved in the regulation of renal tubular function in the opossum. E. coli enterotoxin caused a much larger increase in urine cGMP excretion (10- to 50-fold over control) than did atrial natriuretic factor when these peptides were injected intravenously into opossums. However, atrial natriuretic factor elicited a marked diuresis, natriuresis, and increased urinary excretion of calcium, phosphate, potassium, and magnesium. In contrast, the enterotoxin did not acutely influence OK fluid and electrolyte excretion. Thus the substantial increase in cGMP synthesis produced by the bacterial peptide in OK cortex and medulla in vitro and the increased renal excretion of cGMP in vivo were not associated with changes in electrolyte or water excretion. Whether cGMP represents a second messenger molecule in the kidney is an interesting question that was raised but not answered in this series of experiments.
Forte
L R
LR
Department of Pharmacology, School of Medicine, University of Missouri, Columbia.
Krause
W J
WJ
Freeman
R H
RH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D004768:Enterotoxins / Q000378:metabolism* / Q000494:pharmacology; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide
D001427:Bacterial Toxins; D004573:Electrolytes; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C034151:heat stable toxin (E coli); D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP