A neurosecretory granule Lys-Arg Ca(2+)-dependent endopeptidase putatively involved in prooxytocin and provasopressin processing

A Ca(2+)-dependent endopeptidase cleaving at the carboxyl side of the paired Lys-Arg residues has been found in the neurosecretory granules of the rat neurointermediate pituitary. The specificity pattern on synthetic fluorogenic substrates, the inhibitor profile, the pH optimum of 5.0 and the Ca(2+)-dependence are compatible with an involvement of this enzyme in the prooxytocin and the provasopressin processing within the granules. The enzymatic features of the neurohypophysial granule endopeptidase resemble those of the insulinoma granule type II endopeptidase and suggest that the same Ca(2+)-dependent protease or closely related enzymes could be involved in processing Lys-Arg-containing prohormones in neuroendocrine cells.