T-kinin (Ile-Ser-bradykinin), a previously undescribed peptide, has recently been discovered by our laboratory as a vasoactive peptide released by trypsin from rat plasma. New high performance liquid chromatography technology, as developed in our laboratory, was pivotal to the finding of T-kinin whose precursor is present in very high concentrations in rat plasma. Studies are proposed to investigate the pharmacology of T-kinin and some of its D-analogues since T-kinin is unique as a natural homolog of bradykinin; it does not contain Lys-bradykinin which is part of all known homologs of bradykinin. Its actions on isolated smooth muscle, as a permeability factor, on aspects of the cardiovascular system and as an activating agent for prostaglandin release will be investigated. Its precursor protein, """"""""T-kininogen"""""""", will be studied in terms of its relationship to HMW and LMW kininogens as well as leukokininogen in various species and in normal and pathological states so as to place the T-kinin-T-kininogen system in appropriate relationship to the kallikrein-brady-kinin system. This is of particular importance in the rat since many investigations with kinin generating systems are carried out in this animal; however T-kinin may represent a previously undiscovered kinin system in many species including humans. Patients which have known defects in HMW-kininogen (Williams and Reid traits) will be studied as to their presence of T-kininogen as a """"""""substitute"""""""" kininogen. Purification of T-kininogen will be attempted so as to use the protein as a potential substrate for release of T-kinin by known endogenous proteases. Studies on newly developed methodology using HPLC for the identification and quantitation of kinins and their metabolites will continue.
