ENDOTHELIAL DESQUAMATING ACTIVITY OF RAT SYNTHETIC FIBRINOPEPTIDE-B AND ITS ANALOGS IN-VIVO - IDENTIFICATION OF RESPONSIBLE SEQUENCE

The endothelial desquamating activity of the synthetic rat fibrinopept ide B (ATTDSDKVDLSIAR-OH), and its analogues was studied ''in vivo'' a fter intravenous administration to rats. Rat fibrinopeptide B (FPB) ca used a significant increase in the count of circulating endothelial ce ll carcasses at the dose of 100 nmol/kg. Maximal effect reaching about 270% of the normal value was achieved with the dose of 600 nmol/kg in 30 min. after the injection. No significant thrombocytopenia, no hemo lysis and no other life-threatening complications were observed. The s ame endothelial desquamating effect was achieved with N-terminal FPB ( 1-7) peptide ATTDSDK-OH, but very low activity exhibited the two FPB m utant peptides: ATDSDKVDLSIAR-OH and ATTNSNK-OH. Our results indicate that N-terminal sequence (1-7) consisting of N-terminal ''pig tail'' ( ATT), acid region (DSD) and basic aminoacid (K) is responsible for end othelial desquamating activity of rat FPB. Similar corresponding seque nces may be recognized in FPB of different species. The conservation o f this common ''active site'' sequence is less apparent in primates.