Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation.
The blood-brain barrier is capable of transporting peptides with anti-opiate (Tyr-MIF-1) and opiate (enkephalins) activity out of the central nervous system. The relationship of this transport system to the various actions of opiates remains unexplored. This study examined the relationship between the rate of transport and opiate-induced analgesia. Both restraint, a stress that provokes an opiate-mediated analgesia, and the administration of morphine (12 mg/kg, i.p.) each induced an inhibition in the rate of transport. Such inhibition exhibited specificity, since the saturable, brain to blood transport of iodide remained unaltered. However, it was possible to dissociate analgesia and inhibition of transport. The onset and peak of analgesia, as measured by tail-flick latency induced by morphine, preceded the onset and peak of the inhibition of transport. Naltrexone, which blocks opiate-mediated analgesia, also induced inhibition of transport without any significant effect on tail-flick latency. (-) Naloxone but not (+) naloxone also weakly inhibited transport. Deprivation of food and water, associated with analgesia possibly mediated by the opiate, beta-endorphin, which is not transported out of the brain by this system, did not alter transport. These results suggest that while inhibition of transport and analgesia may occur together, these events probably represent two separate aspects of the action of opiates, that may even be mediated by separate receptor sites or peptides in the opiate family.
D000818:Animals; D001812:Blood-Brain Barrier; D004745:Enkephalins / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D012149:Restraint, Physical; D013237:Stereoisomerism; D013312:Stress, Physiological / Q000503:physiopathology; D013997:Time Factors; D014868:Water Deprivation / Q000502:physiology
D004745:Enkephalins; D009270:Naloxone; D009020:Morphine; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone