Biosynthesis and degradation of peptides derived from Xenopus laevis prohormones

Abstract

Peptides present in the skin secretion of the South African frog, Xenopus laevis, have been analysed by fast atom bombardment mass spectrometry and h.p.l.c. in the mass range 500-3200 Da. We have investigated the effects of successive glandular secretions induced by noradrenaline injections on these peptide levels and have found that the replenishment of the whole range of peptides is complete within 2-6 days. Intact secretory vesicles free of cellular contaminants contain a relatively large number of peptides with molecular masses in the range 2400-2700 Da. We have termed these peptides primary products or spacer peptides, since they originate from spacer regions of the precursors to xenopsin and caerulein. However, if the secretory vesicles are disrupted during the collection procedure and the solution containing the secretion is kept at room temperature for up to 2 h, relatively little of the larger peptides remain. By comparing the relative levels of the various peptides present in these secretions we have found that the larger peptides are proteolytically cleaved into smaller fragments by a novel cleavage at the N-terminal side of a lysine residue (at Xaa-Lys bonds where Xaa is Leu, Gly, Ala or Lys). Preliminary evidence has been obtained suggesting that the larger intact peptides possess lytic activity whereas the smaller proteolytic fragments appear relatively inactive. This may represent a mechanism by which the secretions are rendered harmless to the frog itself, since prolonged exposure would be expected to result in toxic effects. The dorsal glands of X. laevis thus appear similar to endocrine glands, since they are involved in peptide biosynthesis, secretion and subsequent proteolytic degradation.