Kinin-forming enzyme in rat brain mitochondria fraction and biological activity of a kinin released from rat plasma kininogen by this enzyme.
The kinin-forming enzyme of rat brain was studied by bioassaying kinin using a rat uterus. The enzyme released a kinin from the partially purified kininogen of rat plasma. The activity is exclusively distributed in the mitochondrial fraction and was detected in the pH range of 2.5-4.0 (optimally at pH 3.0). The enzyme was potently inhibited by pepstatin, but not by aprotinin. Released kinin was extracted by n-butanol and it was purified using Amberlite CG-50 absorption and CM-cellulose column chromatography. The elution profile of kinin from the CM-cellulose column did not coincide with that of bradykinin, Lys-bradykinin or Met-Lys-bradykinin. Isolated kinin was inactivated by treatment with chymotrypsin, but not with trypsin. In addition to the contractile activity on rat uterus, the kinin caused contraction of guinea pig ileum, with the response being potentiated by the presence of bradykinin-potentiator B. It also relaxed a rat duodenum, decreased rat blood pressure, and increased the vascular permeability in guinea pigs. Relative potencies of kinin on these pharmacological activities did not coincide with those of bradykinin. From these results, it is concluded that a kinin-forming enzyme is present in the rat brain. It is a cathepsin D-like enzyme, and furthermore, the enzyme releases a kinin-like peptide from the plasma kininogen fraction.
D020001:1-Butanol; D000818:Animals; D001921:Brain / Q000201:enzymology*; D000440:Butanols / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007705:Kinins / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism
D000440:Butanols; D007705:Kinins; D011480:Protease Inhibitors; D020001:1-Butanol; D002918:Chymotrypsin; D014357:Trypsin