Precursors of Vasopressin and Oxytocin

Abstract

Publisher Summary It is now known that in addition to transcription and translation processes, various signal sequences and post-translational processing events are also involved in determining the type of peptides that are secreted by the cell. This chapter describes unequivocal criteria for the identification of precursors of peptides with regard to both vasopressin and oxytocin. These criteria include (1) demonstration in classical pulse-chase experiments in intact cellular systems that a larger form of the peptide is first synthesized and subsequently decreases in radioactivity as the radioactive peptide is formed, (2) demonstration by in vitro translation experiments that a larger precursor form of the peptide is synthesized, and (3) utilizing modem recombinant DNA techniques to clone cyclic DNA (cDNA) obtained from a purified messenger RNA (mRNA) template using reverse transcriptase. A variety of biosynthesis studies conducted in vivo and in vitro have shown that the vasopressin precursor is a 19–23,000 molecular weight glycoprotein, which contains vasopressin at its N-terminus, neurophysin in the middle, and a 39 amino acid glycopeptide at the C-terminus. While, the 15–16,000 molecular weight oxytocin precursor is not glycosylated. The vasopressin precursor has been completely sequenced by recombinant DNA methods, thereby providing insights into the nature of the glycopeptide as well as post-translational processing mechanisms. However, many questions remain to be answered such as the nature of the post-translational processing enzymes and mechanisms that fashion the final peptide products or the mechanisms underlying the transcriptional and translational regulation of the precursors during functional activity.