Inactivation of atrial natriuretic substance by kallikrein.
To further characterize the properties of the potent natriuretic and diuretic substance that can be extracted from atrial tissue, we investigated its susceptibility to inactivation by kallikrein and other proteolytic enzymes. Extracts of rat atrial tissue (tissue wet wt 100 mg/ml) were incubated with enzymes under standard conditions and tested by injection into nondiuretic anesthetized rats. One hour of incubation at 37 degrees C with pure porcine pancreatic kallikrein at concentrations of 250 micrograms/ml or greater significantly reduced the activity of atrial natriuretic substance. The reduction in activity was dependent on both enzyme concentration and time of incubation. The kallikrein-catalyzed degradation was completely blocked by aprotinin but was only partially retarded by soybean trypsin inhibitor. Trypsin reduced natriuretic and diuretic activity of extracts at concentrations of 400 micrograms/ml or greater, with nearly complete inactivation at a concentration of 1,000 micrograms/ml. Carboxypeptidase B also caused a concentration-dependent inactivation of the natriuretic material. Last, alpha-chymotrypsin (1,000 micrograms/ml) and elastase (1,000 micrograms/ml) were found to destroy the natriuretic activity. In a separate set of experiments natriuretic activity was observed to be retained by a 1,000 mol wt cutoff membrane. Inactivation of the natriuretic peptide by renal kallikrein is a possible mechanism for in vivo regulation of natriuretic activity.
D000818:Animals; D009320:Atrial Natriuretic Factor; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D006325:Heart Atria / Q000032:analysis; D007610:Kallikreins / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000502:physiology*; D010196:Pancreatic Elastase / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000502:physiology; D014357:Trypsin / Q000494:pharmacology; D014462:Ultrafiltration
D009124:Muscle Proteins; D014020:Tissue Extracts; D009320:Atrial Natriuretic Factor; D002268:Carboxypeptidases; D043424:Carboxypeptidase B; D007610:Kallikreins; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D014357:Trypsin