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

Processing endopeptidase deficiency in neurohypophysial secretory granules of the diabetes insipidus (Brattleboro) rat

The homozygote Brattleboro rat exhibits a hereditary diabetes insipidus due to a deficiency of vasopressin, the antidiuretic hormone. It has previously been shown that in this animal a single nucleotide deletion in the provasopressin gene leads to a mutant precursor with a C-terminal amino acid sequence different from that of the wild-type. However the N-terminal region including the hormone moiety, the processing signal as well as the first two-thirds of the neurophysin is entirely preserved and absence of maturation has to be explained by an additional cause. We show here that the neurohypophysis of the homozygote Brattleboro rat, in contrast to the adenohypophysis, displays a significant decrease in the Lys-Arg processing endopeptidase activity when compared to the heterozygote or the wild-type Wistar. It is suggested that hypothalamic vasopressinergic neurons of the homozygote Brattleboro rat display a deficiency in the processing enzyme in contrast to the oxytocinergic neurons in which processing of prooxytocin is normal