Conversion and release of an intermediate in vasopressin–neurophysin biosynthesis in the guinea-pig

Abstract

ABSTRACT Guinea-pig neural lobes contain appreciable amounts of neurophysin with a glycopeptide extension (NPGP) which may represent a partially processed form of the arginine vasopressin (AVP) precursor. We have now studied the turnover and release of the NPGP component using a combination of in-vivo radiolabel incorporation and high pressure liquid chromatography. Measurement of the neural lobe content of 35S-labelled peptides at various times after hypothalamic injection of [35S]cysteine demonstrated that the oxytocin-related products accumulated more rapidly than the AVP-related products. The relative amounts of [35S]cysteine incorporated into NPGP and the AVP-related neurophysin (NPavp) changed markedly with time after in-vivo labelling. In-vitro incubation of neurosecretory granules prepared from neural lobes 4 h after radiolabel injection produced a time- and temperature-dependent conversion of NPGP to NPavp. Incubation at 37 °C for 4 h produced a 30% decrease in [35S]NPGP with a concomitant increase in [35S]NPavp, whilst there were no changes in the other 35S-labelled components. In-vitro stimulation of radiolabelled neural lobes by 56 mm-K+ evoked a Ca++-dependent release of NPGP as well as the other expected neurosecretory components, and the amount of NPGP released reflected its neural lobe content. We conclude that the NPGP component found in guinea-pig neural lobes is a biosynthetic intermediate, most of which is further processed to NPavp. However, some NPGP may also be secreted from the neural lobe in an intact form. J. Endocr. (1984) 103, 347–354