Blunting effect of pepsanurin introduced in the duodenum on the atrial natriuretic peptide diuretic action in rats.
Pepsanurin (PU) is a peptide(s) obtained by pepsin hydrolysis of human plasma or its globulin fraction. We have reported that the accelerated renal excretory rate induced by atrial natriuretic peptide (ANP) can be considerably blunted by PU either in the intact rat or in the isolated perfused rat kidney. We explored whether or not PU can be part of a signaling mechanism originated in the digestive tract, involved in the regulation of water and electrolyte homeostasis. PU obtained either from human (0.5 ml) or rat plasma (0.25-0.5 ml) administered into the duodenal lumen of rats, counteracted significantly the diuretic-saluretic action of a 0.5- microgram bolus of ANP, reproducing qualitatively the effect of its intraperitoneal administration. Human PU reduced the ANP-stimulated renal excretion by 67-90% for Na (P < 0.001) and by 35-54% for water (P < 0.02-P < 0.001); the inhibition induced by rat PU was 45-96% for Na (P < 0.05-P < 0.01) and 35-65% for water (P < 0.05-P < 0.01). Rat PU (0.5 ml) abolished the rise of glomerular filtration rate induced by ANP without affecting fractional Na excretion. All the samples tested decreased K excretion, but in some experiments, the difference did not reach statistical significance. Contrary to the effect of PU, the introduction in the duodenum of (i) isotonic glucose solution, (ii) hydrolysate of bovine serum albumin, or (iii) hydrolysate of casein prepared after the same procedure yielding PU from plasma failed to produce an inhibition of the ANP stimulation of renal excretory rate. In addition, human plasma incubated at 37 degrees C for 24 to 48 hr, prior to pepsin digestion, did not yield PU, which indicates that PU is generated from a substrate sensitive to endogenous enzymes and/or that its stability is vulnerable to endogenous enzymes.
Croxatto
H R
HR
Unidad de Regulación Neurohumoral, Facultad Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago.
Borić
M P
MP
Roblero
J S
JS
Albertini
R
R
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001681:Biological Assay; D001794:Blood Pressure; D002364:Caseins / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012964:Sodium / Q000652:urine; D014882:Water-Electrolyte Balance / Q000187:drug effects
D002364:Caseins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C058006:pepsanurin; D012710:Serum Albumin, Bovine; D009320:Atrial Natriuretic Factor; D012964:Sodium; D005947:Glucose; D011188:Potassium