Altered processing of pro-orphanin FQ/nociceptin and pro-opiomelanocortin-derived peptides in the brains of mice expressing defective prohormone convertase 2.

摘要: The bioactivity of neuropeptides can be regulated by a variety post-translational modifications, including proteolytic processing. Here, gene-targeted mice producing defective prohormone convertase 2 (PC2) were used to examine the processing two neuroendocrine prohormones, pro-opiomelanocortin (POMC) and pro-orphanin FQ (pOFQ)/nociceptin (N), in brain. Reversed-phase HPLC gel-exclusion chromatography combined with specific radioimmunoassays analyze patterns these prohormones hypothalamus amygdala. In case POMC, lack PC2 activity completely prevented carboxy-shortening β-endorphins greatly diminished conversion β-lipotropin γ-lipotropin β-endorphin. Although β-endorphin decreased, caused an increase levels mutant animals, but no increases POMC or biosynthetic intermediates seen. extent OFQ/N production was significantly lower PC2-deficient there accumulation relatively large amounts pOFQ/N intermediates. These results demonstrate that is directly involved biogenesis brain vivo suggest cellular context influences neuropeptide PCs.