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.