title: Kinin-forming activity in rat brain.
abstract: The present study shows that rat brain contains a kinin-forming activity which is distinguishable from plasma kallikrein. Kinin-forming activity was found in an acetone powder of frozen brain tissue (between 27 and 175.5 ng generated bradykinin/g fresh brain tissue/h). Analysis by high pressure liquid chromatography (HPLC) indicated that the kinin formed chromatographed like true bradykinin (BK). After subcellular fractionation using differential centrifugation of homogenized fresh brain tissue the kinin-forming activity was found mainly in a microsomal (P-3) fraction after preincubation with 2 ?M melittin. Further fractionation of P-3 fraction using discontinuous sucrose gradient centrifugation identified activity in both the 1 M sucrose layer (5.8 +/- 3.1 ng kinin/mg protein/h) and at the interface between the 0.8 and 0.3 sucrose layers (9.4 +/- 4 ng kinin/mg protein/h). Melittin pretreatment did not change these values. The distribution pattern of the kallikrein-like activity was different from that of cathepsin d-like acid protease. The two kinin-forming activities were equally sensitive to treatment with various trypsin inhibitors but were clearly distinguishable from plasma kallikrein: brain activity was inhibited completely by Trasylol but not by soybean trypsin inhibitor (SBTI) or ovomucoid while plasma kallikrein was completely inhibited by SBTI and partially by ovomucoid and Trasilol. Our results clearly distinguish between plasma kallikrein, brain cathepsin d-like acid protease activity and an apparent brain kinin-forming activity, but do not by themselves establish a central biosynthetic pathway for kinin generation.
authors.affiliation: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 6900 Heidelberg, F.R.G.
authors.forename: A C
authors.initials: AC
authors.lastname: Shisheva
authors.forename: M P
authors.initials: MP
authors.lastname: Printz
authors.forename: K
authors.initials: K
authors.lastname: Herman
authors.forename: D
authors.initials: D
authors.lastname: Ganten