Abstract
Peptides of the NPY family are synthesized as large precursor molecules in the endoplasmatic reticulum (ER), where posttranslational modification takes place, and from where they are translocated to the Golgi apparatus. After several structural and functional adjustments, two types of mature vesicle—large dense core vesicles and synaptic vesicles—serve as a storage depot. Notably, the expression of a gene for a peptide from the NPY family is not sufficient to ensure the production of mature peptides since several posttranslational steps are specifically involved and these steps themselves are subjected to specific regulatory processes. Similarly, after exocytotic release of NPY-like peptides, their local action depends on their concentration, their different receptor selectivity and the local expression of the different Y-receptors. Another major player in this complex network is found in the action of specific peptidases influencing half-life and receptor selectivity. At least aminopeptidase P, dipeptidyl-peptidase IV-like enzymes, specific endopeptidases, like meprin or neprilysin-like enzymes, and post-arginine hydrolyzing endoproteases are cleaving enzymes for NPY-like peptides. Due to a striking change of receptor specificity after N-terminal cleavage of NPY-like peptides, the development of inhibitors for NPY, PYY and PP cleaving peptidases is a complementary approach to the development of Y-receptor agonists or antagonists. In this chapter, we summarize key findings about synthesis, storage, release and localization of NPY family peptides, add recent findings on their degradation by specific enzymes and discuss implications for the interpretation of studies in future research.
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von Hörsten, S. et al. (2004). PP, PYY and NPY: Synthesis, Storage, Release and Degradation. In: Michel, M.C. (eds) Neuropeptide Y and Related Peptides. Handbook of Experimental Pharmacology, vol 162. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18764-3_2
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