Kallikrein activation of a high molecular weight atrial peptide.
Mammalian atrial extracts contain bioactive peptides that exert profound effects upon renal function and isolated smooth muscle preparations. Gel filtration chromatography of rat atrial extract separates the activity into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. Mild proteolytic treatment (trypsin 1 U/ml) of the high molecular weight fraction enhances the smooth muscle relaxant activity of this fraction and concomitantly reduces the apparent molecular weight of this fraction to less than 10,000. In this report we show that urinary and submaxillary kallikrein enhances the activity of rat atrial extracts in a similar fashion. Pretreatment of the high molecular weight fraction with either kallikrein (1 microgram/ml) enhances the smooth muscle relaxant activity of this fraction. Similar treatment of the low molecular weight fraction had no effect. The enhancement of the bioactivity of the high molecular weight substance(s) by the kallikreins was abolished by aprotinin but was unaffected by soybean trypsin inhibitor. These results suggest that exogenous addition of tissue kallikrein activates a high molecular weight peptide by limited proteolysis. Analysis of the kallikrein-treated high molecular weight peptide fraction by gel filtration indicates that the biological activity comigrates with the low molecular weight peptides present in the original atrial extract.
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor; D001681:Biological Assay; D002645:Chickens; D006325:Heart Atria / Q000032:analysis*; D007610:Kallikreins / Q000494:pharmacology*; D008970:Molecular Weight; D009124:Muscle Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D011498:Protein Precursors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014357:Trypsin / Q000494:pharmacology
D009124:Muscle Proteins; D011498:Protein Precursors; D009320:Atrial Natriuretic Factor; D007611:Aprotinin; D007610:Kallikreins; D014357:Trypsin