Membrane leakage induced by dynorphins.
Dynorphins, endogeneous opioid peptides, function as ligands to the opioid kappa receptors and induce non-opioid excitotoxic effects. Here we show that big dynorphin and dynorphin A, but not dynorphin B, cause leakage effects in large unilamellar phospholipid vesicles (LUVs). The effects parallel the previously studied potency of dynorphins to translocate through biological membranes. Calcein leakage caused by dynorphin A from LUVs with varying POPG/POPC molar ratios was promoted by higher phospholipid headgroup charges, suggesting that electrostatic interactions are important for the effects. A possibility that dynorphins generate non-opioid excitatory effects by inducing perturbations in the lipid bilayer of the plasma membrane is discussed.
Hugonin
Loïc
L
Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, S-10691 Stockholm, Sweden.
Vukojević
Vladana
V
Bakalkin
Georgy
G
Gräslund
Astrid
A
D000595:Amino Acid Sequence; D004399:Dynorphins / Q000737:chemistry*; D004723:Endorphins / Q000737:chemistry*; D005452:Fluoresceins / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry
D004723:Endorphins; D005452:Fluoresceins; D008081:Liposomes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D004399:Dynorphins; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C036200:rimorphin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C007740:fluorexon