ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESIS

Project Details

Description

Dynorphins are a class of very potent opioid peptides with wide distribution in the central and peripheral nervous systems. Dynorphins may act both as neurotransmitters or neuromodulators in brain and as hormones in the endocrine system. They are thought to be involved in pain perception, intestinal peristalsis, feeding and sleep. Dynorphins are synthesized as a precursor protein, prodynorphin, that through limited proteolysis by trypsin-like and carboxypeptidase B-like enzymes gives rise to alpha- and beta-neoendorphin. dynorphins A, A-8 and B, leumorphin, and leucine-enkephalin. These prodynorphin derived peptides bind to the various opiate receptors with different affinities, and so the processing enzymes play a key role in the modulation of opioid gene expression. However, little is known about the endopeptidase processing enzymes. The objective of this study will be to purify and characterize a novel enzyme involved in prodynorphin processing. A dynorphin processing enzyme that acts at a monobasic cleavage site has previously been reported Further studies described in this proposal include: purification and characterization of the enzyme, cellular and subcellular localization, development of site-directed inhibitors, and development of monoclonal and/or polyclonal antibodies. Regulation of this enzyme will be examined in several neural and endocrine cell lines. Information gained through these studies on the processing enzymes should serve not only as a basis for future investigations of dynorphin synthesis but also should aid in the study of other neuropeptide processing pathways.
StatusFinished
Effective start/end date1/08/8931/07/94

Funding

  • National Institute of Neurological Disorders and Stroke

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