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

Sloan, Courtney D. Kuhnline; Audus, Kenneth L.; Aldrich, Jane V.; Lunte, Susan M.

doi:10.1016/j.peptides.2012.09.031

Cited by 4 publications

(1 citation statement)

References 19 publications

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“…Dynorphin A (Dyn A) is an endogenous opioid peptide that is derived from the precursor peptide preprodynorphin . This peptide has high affinity for the κ‐opioid receptor . Dyn A has been found to exhibit both antinociceptive and analgesic effects within the central nervous system and is also involved in the body's immune response as well as cardiovascular and temperature regulation .…”

Section: Introductionmentioning

confidence: 99%

Separation of dynorphin peptides by capillary electrochromatography using a polydiallyldimethylammonium chloride gold nanoparticle‐modified capillary

2016

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Dynorphin A (Dyn A) is an endogenous opioid peptide found in blood and CNS tissue at very low concentrations. Elevated levels of Dyn A due to different disease states, for example, neurodegenerative disease, have been linked to toxic nonopioid activity. Capillary electrophoresis (CE) is a powerful technique that can achieve high efficiency separations of charged analytes. However, CE has limited use for the analysis of basic proteins and peptides, due to their adsorption onto the inner surface of the fused silica at pHs below their pI. This adsorption can lead to a loss of efficiency, irreproducibility of migration times, and peak tailing. To obviate this problem, a polydiallyldimethylammonium chloride-stabilized gold nanoparticle-coated capillary was investigated for the separation of dynorphin metabolites. The positively charged gold nanoparticles (GNP) minimized unwanted adsorption of the positively charged peptides onto the surface of the fused silica capillary. Separation efficiency and resolution for opioid peptides Dyn A (1-6), Dyn A (1-7), Dyn A (1-8), Dyn A (1-11), and leu-enkephalin on the GNP-coated capillary column were evaluated under different experimental parameters. The best separation of Dyn A (1-17) and its fragments was achieved using a background electrolyte that consists of 40 mM sodium acetate buffer (pH 5) containing 5% GNP, a field strength of −306 V/cm, and a 75 μm i.d. capillary. The developed method was applied to the separation of tryptic peptide fragments of dynorphin A (1-17).

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Section: Introductionmentioning

confidence: 99%

Separation of dynorphin peptides by capillary electrochromatography using a polydiallyldimethylammonium chloride gold nanoparticle‐modified capillary

2016

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Endogenous opiates and behavior: 2012

Bodnar

2013

Peptides

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Re-evaluation of the role of P-glycoprotein inin vitrodrug permeability studies with the bovine brain microvessel endothelial cells

Hakkarainen¹,

Rilla²,

Suhonen³

et al. 2013

Xenobiotica

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1. Currently available in vitro blood-brain barrier models all have recognized restrictions. In addition to leakiness, inconsistent data about P-glycoprotein mediated efflux limit the attractiveness of the primary bovine brain microvessel endothelial cells (BBMECs). Therefore, we re-evaluated the role of P-glycoprotein mediated efflux with two culture conditions in BBMECs for prediction of drug permeability of potential P-glycoprotein substrates. 2. BBMECs were monocultured on filters on petri dishes and on filter inserts, and expression and localization of P-glycoprotein were compared by using western blot and confocal microscopy, respectively. The functionality of P-glycoprotein was assessed by using cellular uptake, calcein-AM and bidirectional transport assays. 3. P-glycoprotein expression was higher in BBMECs cultured on filter inserts decreasing the permeability of digoxin and paclitaxel, but not the permeability of vinblastine. However, the monocultured BBMECs were not able to demonstrate efflux in the bidirectional transport assays. Under certain culture conditions, occludin may not be correctly located, perhaps explaining in part the leakiness of BBMECs. 4. In conclusion, BBMECs, despite possessing a functional P-glycoprotein, under certain culture conditions may not be a suitable in vitro model for the bidirectional transport assays and for predicting the permeability of drugs and xenobiotics that are potential P-glycoprotein substrates.

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

Cited by 4 publications

References 19 publications

Separation of dynorphin peptides by capillary electrochromatography using a polydiallyldimethylammonium chloride gold nanoparticle‐modified capillary

Separation of dynorphin peptides by capillary electrochromatography using a polydiallyldimethylammonium chloride gold nanoparticle‐modified capillary

Endogenous opiates and behavior: 2012

Re-evaluation of the role of P-glycoprotein inin vitrodrug permeability studies with the bovine brain microvessel endothelial cells

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