Metabolism of dynorphins by peptidases of pulmonary artery endothelial cells

Degradation of several dynorphins by peptidases expressed in cultured porcine pulmonary artery endothelial cells was studied by incubation of the peptide in cell suspensions followed by electrospray ionization and tandem mass spectrometric analyses. Under the in vitro conditions applied, only the metabolism of dynorphin A_1-8 occurred in a significant extent Studies involving specific peptidase inhibitors indicated that mainly bestatin-sensitive amino-peptidases, thiorphan-sensitive endopeptidases, and cFPAAF-pAB-sensitive endopeptidases expressed by the endothelial cells were involved in the process that converted dynorphin A_1-8 to dynorphin A_2-8, dynorphin A_1-6, and leucine enkephalin (dynorphin A_1-5), respectively. These peptidases may form a metabolic barrier for the cellular penetration of intact dynorphin A_1-8 and/or control effects of the circulating peptide on endothelial opioid receptors of the cells.