delta 1-Opioid receptor-mediated control of acetylcholine (ACh) release in human neocortex slices.
In slices of human neocortex, prelabelled with [3H]-choline, the release of [3H]-acetylcholine reflects the evoked release of endogenous acetylcholine which was elicited by the same electrical stimulation paradigm. [3H]-Acetylcholine release was depressed by the delta-opioid receptor agonist D-Pen2-D-Pen5-enkephalin. When the nerve endings were depolarized by elevating extracellular potassium the evoked [3H]-acetylcholine release was similarly depressed by D-Pen2-D-Pen5-enkephalin in the absence, but not in the presence, of tetrodotoxin which blocks action potential propagation. Therefore, the delta-opioid receptor inhibiting [3H]-acetylcholine release should not be located to cholinergic nerve terminals, but rather to interneurons. The somatostatin2 receptor partial agonist octreotide per se did not influence action potential-evoked [3H]-acetylcholine release, but prevented the inhibition of release of [3H]-acetylcholine by D-Pen2-D-Pen5-enkephalin. Similarly, the delta 1-opioid receptor antagonist 7-benzylidenenaltrexon per se did not influence [3H]-acetylcholine release, but prevented of the inhibition of release by D-Pen2-D-Pen5-enkephalin. From the present findings we conclude: (1) The evoked release of [3H]-acetylcholine from human neocortex slices reflects the release of endogenous acetylcholine. (2) It is inhibited in an indirect manner by opioid receptors of the delta 1-subtype, which (3) are not localized on cholinergic axon terminals but on soma and dendrites of somatostatin-containing interneurons, where they inhibit somatostatin release. (4) These interneurons innervate cholinergic nerve endings in the human neocortex and appear to facilitate acetylcholine release via somatostatin2 receptors.
Feuerstein
T J
TJ
Sektion Klinische Neuropharmakologie, Neurologischen Universitätsklinik, Neurozentrum, Freiburg, Germany. feuer@ukl.uni-freiburg.de
Albrecht
C
C
Wessler
I
I
Zentner
J
J
Jackisch
R
R
D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001597:Benzylidene Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019579:Neocortex / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001597:Benzylidene Compounds; D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C077358:7-benzylidenenaltrexone; D013779:Tetrodotoxin; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole; D000109:Acetylcholine; D015282:Octreotide