PEPTIDASES IN THE CNS - FORMATION OF BIOLOGICALLY-ACTIVE, RECEPTOR-SPECIFIC PEPTIDE-FRAGMENTS

Peptides function as chemical signals between cells of multicellular o rganisms, or different organisms, via specific receptors on target cel ls. Many hormones, neuromodulators, and growth factors are peptides. B ecause there is no known reuptake system for peptides at the nerve ter minal, the biological activity of peptides in the extracellular space is regulated by enzymatic degradation and extracellular metabolism. Fo r example, angiotensin I is processed extracellularly in the lung by a ngiotensin-converting enzyme (ACE; E.C.3.4.15.1), a peptidyl dipeptida se, to form the potent vasoconstrictor hormone angiotensin II. When ne uropeptides are released from neurons into the extracellular space, sp ecific peptidases also can modulate the peptidergic signal by generati ng smaller, biologially 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 extracellula r regulation of peptidergic signaling, alterations in peptidase activi ties 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, re ceptor-specific peptides from peptide E, beta-endorphin, neurotensin, and cholecystokinin.