Penetration of dynorphin 1-13 across the blood-brain barrier.
Previous studies have demonstrated neuroprotective effects of the opioid peptide dynorphin (dyn) 1-13 in focal cerebral ischemia. The passage of dyn 1-13 across the blood-brain barrier (BBB) was studied by a modification of the Oldendorf technique in the normal rat and cat, as well as in a feline model of experimentally induced focal cerebral ischemia. In the rat, dyn 1-13 penetration of the BBB could not be detected by this technique, even in the presence of peptidase inhibitors. In contrast, dyn 1-13 did cross the BBB into the normal cat hippocampus, cortex and cerebellum. The passage of dyn 1-13 across the BBB was greater in cats with experimentally induced focal cerebral ischemia. Some of the tritium-labeled material which crossed the BBB was confirmed by high performance liquid chromatography to be dyn 1-13. These studies support the hypothesis that the therapeutic effects observed after the peripheral administration of dyn 1-13 to cats with focal cerebral ischemia can be produced by a central mechanism of action.
Turner
T D
TD
Neurosurgery Section, Department of Surgery, Veterans Affairs Medical Center, Houston, TX 77030, USA.
Browning
J L
JL
Widmayer
M A
MA
Baskin
D S
DS
D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000493:pharmacokinetics; D007611:Aprotinin / Q000493:pharmacokinetics; D001414:Bacitracin / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000502:physiology*; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004399:Dynorphins / Q000493:pharmacokinetics*; D007930:Leucine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D018696:Neuroprotective Agents / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000493:pharmacokinetics; D014443:Tyrosine / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D001414:Bacitracin; D014443:Tyrosine; D013395:Sucrose; C026843:dynorphin (1-13); D004399:Dynorphins; D007611:Aprotinin; D007930:Leucine; C012211:ubenimex