PROTEOLYTIC CONVERSION OF OXYTOCIN INVIVO AFTER MICROINJECTION IN THERAT HIPPOCAMPUS

Since previous studies in vivo' have shown that oxytocin is metabolize d by rat synaptic membrane-bound aminopeptidase- and endopeptidase-lik e enzymes, the proteolytic conversion of oxytocin was studied in vivo after microinjection in the rat hippocampus, a brain area that contain s oxytocinergic nerve endings and receptors. Isolation of the formed p eptide fragments from the injected brain area after homogenization and adsorbtion on a Sep-Pak cartridge by high performance liquid chromato graphy, and their characterization by amino acid analysis, revealed th at, when oxytocin (50 nmol in 0.5 mul) was microinjected in the CA1 fi eld of the rat hippocampus, only the N-terminal fragment oxytocin(1-8) was formed in such amount that could be characterized. The microinjec tion of [H-3-Tyr2]oxytocin (10 pmol) revealed that in addition to oxyt ocin(1-8), free [H-3]tyrosine was formed. Taken together with previous findings showing that C-terminal oxytocin fragments as well oxytocin( 1-8) are formed by membrane-bound aminopeptidases and endopeptidases i n vitro, respectively, the results suggest that, in addition to aminop eptidases, endopeptidase-like enzymes are involved in the proteolysis of endogenous brain oxytocin.