[Naloxone-resistant EEG slowing induced by the synthetic opioid peptide FK 33-824 in the 4th cerebral ventricle of the dog].
In order to determine the importance of opioid peptides in the central control of wakefulness, the synthetic analogue of Met-Enkephalin, FK 33-824 (d-Ala-2-Phe-Met-(O)-ol-Enkephalin) which is more resistant to enzymatic degradation, was perfused in increasing concentrations (20, 100, 200, and 400 micgrograms/ml) through the fourth cerebral ventricle of the conscious dog. In the EEG (Power-spectral density in continuous acquisition) high concentrations (200--400 micgrograms/ml) induce slowing (theta--delta) with overlying beta-activity. This was reflected in the animals behaviour resulting in a sleep-like state which in spite of the administration of high doses of the antagonist Naloxone (100 micrograms/kg i.v.) sustained for 12 hours. A simultaneously dose-related respiratory depression (drop in arterial pO2 and an increase in arterial pCO2) was reversed by Naloxone. It is concluded that the opioid peptide FK 33-824 induces EEG-slowing which is mediated by a subpopulation of opiate-binding sites, possibly the kappa-receptors. These receptors are different from binding sites mediating respiratory depression (micro-receptors) as they interact with the opiate-antagonist Naloxone.
D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D007276:Injections, Intraventricular; D009270:Naloxone / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D006728:Hormones; D011957:Receptors, Opioid; D009270:Naloxone; D004744:Enkephalin, Methionine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin
Naloxon-resistente EEG-Verlangsamung, bedingt durch das synthetische Opioid-Peptid FK 33-824 im IV. Hirnventrikel des Hundes.