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Cathepsin L Participates in the Production of the Dynorphin Opioid Peptide Neurotransmitter
Author(s) -
Minokadeh Ardalan,
Toneff Thomas,
Funkelstein Lydiane,
Reinheckel Thomas,
Peters Christoph,
Zadina James,
Hook Vivian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.671.3
Subject(s) - dynorphin , opioid peptide , chemistry , neuropeptide , cathepsin , dynorphin a , cathepsin b , cathepsin l , cathepsin s , endocrinology , medicine , microbiology and biotechnology , biology , opioid , biochemistry , receptor , enzyme
Dynorphins, as well as other opioid neuropeptides, have an established role in analgesia and pain processing among other central nervous system functions. Dynorphin neuropeptides, as well as numerous peptide neurotransmitters, are generated by proteolytic processing of respective proneuropeptide precursors. Processing of proneuropeptides has recently been found to be mediated by the recently discovered cathepsin L cysteine protease in secretory vesicles. To assess the role of secretory vesicle cathepsin L in dynorphin production, studies in cathepsin L gene knockout mice and with cathepsin L protease expression were conducted. In brains of cathepsin L gene knockout mice, substantial reduction of prodynorphin‐derived neuropeptides was observed. Brain levels of dynorphin A, dynorphin B, and a‐neoendorphin were decreased by more than 70% in cathepsin L knockout mice compared to wild‐type. Expression of cathepsin L with prodynorphin in neuroendocrine PC12 cells resulted in increased production of dynorphin A, indicating cathepsin L mediated conversion of prodynorphin to the dynorphin peptide product. Moreover, colocalization of dynorphins with cathepsin L in secretory vesicles of neuronal cells was demonstrated by immunofluorescence confocal microscopy. These results demonstrate a significant role for secretory vesicle cathepsin L in the produciton of dynorphin opioid neuropeptides.