Deltorphin transport across the blood-brain barrier.
In vivo antinociception studies demonstrate that deltorphins are opioid peptides with an unusually high blood-brain barrier penetration rate. In vitro, isolated bovine brain microvessels can take up deltorphins through a saturable nonconcentrative permeation system, which is apparently distinct from previously described systems involved in the transport of neutral amino acids or of enkephalins. Removing Na+ ions from the incubation medium decreases the carrier affinity for deltorphins (-25%), but does not affect the Vmax value of the transport. The nonselective opiate antagonist naloxone inhibits deltorphin uptake by brain microvessels, but neither the selective delta-opioid antagonist naltrindole nor a number of opioid peptides with different affinities for delta- or mu-opioid receptors compete with deltorphins for the transport. Binding studies demonstrate that mu-, delta-, and kappa-opioid receptors are undetectable in the microvessel preparation. Preloading of the microvessels with L-glutamine results in a transient stimulation of deltorphin uptake. Glutamine-accelerated deltorphin uptake correlates to the rate of glutamine efflux from the microvessels and is abolished by naloxone.
Fiori
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A
Department of Cellular Biotechnology and Hematology, University "La Sapienza", 00185 Rome, Italy.
Cardelli
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P
Negri
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Savi
M R
MR
Strom
R
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Erspamer
V
V
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D002417:Cattle; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology; D012964:Sodium / Q000502:physiology
D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; C059567:deltorphin; D009270:Naloxone; D012964:Sodium