The permeation of dynorphin A 1–6 across the blood brain barrier and its effect on bovine brain microvessel endothelial cell monolayer permeability

Dynorphin A 1–17 (Dyn A 1–17) is an endogenous neuropeptide known to act at the kappa opioid receptor; it has been implicated in a number of neurological disorders, including neuropathic pain, stress, depression, and Alzheimer's and Parkinson's diseases. The investigation of Dyn A 1–17 metabolism at the blood–brain barrier (BBB) is important since the metabolites exhibit unique biological functions compared to the parent compound. In this work, Dyn A 1–6 is identified as a metabolite of Dyn A 1–17 in the presence of bovine brain microvessel endhothelial cells (BBMECs), using LC–MS/MS. The transport of Dyn A 1–6 at the BBB was examined using this in vitro cell culture model of the BBB. Furthermore, the permeation of the BBB by the low molecular weight permeability marker fluorescein was characterized in the presence and absences of Dyn A 1–6.

► Dynorphin A 1–6 is identified as a metabolite of Dynorphin A 1–17 in the presence of bovine brain microvessel endothelial cells (BBMECs). ► The blood brain barrier (BBB) permeability of the neuropeptide Dyn A 1–6 is investigated using the BBMEC culture model of the BBB. ► The directional and temperature dependent permeation of Dyn A 1–6 is evaluated. ► Dyn A 1–6 pretreatment is found to induce an opening of the BBB, increasing the permeation of fluorescein, a low molecular weight, low permeability control substance.