Peptidases in the CNS: formation of biologically active, receptor-specific peptide fragments.
Peptides function as chemical signals between cells of multicellular organisms, or different organisms, via specific receptors on target cells. Many hormones, neuromodulators, and growth factors are peptides. Because there is no known reuptake system for peptides at the nerve terminal, the biological activity of peptides in the extracellular space is regulated by enzymatic degradation and extracellular metabolism. For example, angiotensin I is processed extracellularly in the lung by angiotensin-converting enzyme (ACE; E.C. 3.4.15.1), a peptidyl dipeptidase, to form the potent vasoconstrictor hormone angiotensin II. When neuropeptides are released from neurons into the extracellular space, specific peptidases also can modulate the peptidergic signal by generating smaller, biologically active fragments via products with similar or dissimilar characteristics of the parent peptide. Therefore, receptor-binding selectivity of a released peptide hormone can be regulated by peptidases. Because peptidases may play a key role in the extracellular regulation of peptidergic signaling, alterations in peptidase activities by drugs or disease states may lead to disruptions in biological homeostasis. The subject of this article is the role of peptidases in the central nervous system in the formation of biologically active, receptor-specific peptides from peptide E, beta-endorphin, neurotensin, and cholecystokinin.
Davis
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University of Arizona, College of Medicine, Department of Pharmacology, Tucson 85724.
Konings
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PN
D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000096:biosynthesis / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
D004745:Enkephalins; D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D009496:Neurotensin; D001615:beta-Endorphin; C033660:preproenkephalin; D010450:Endopeptidases