Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors.
In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, The Netherlands.
A N
AN
Schoffelmeer
G
G
Warden
F
F
Hogenboom
A H
AH
Mulder
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin / Q000494:pharmacology*
D004745:Enkephalins; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine; D009270:Naloxone; D001615:beta-Endorphin; D009638:Norepinephrine