delta(1)-opioid receptor-mediated control of acetylcholine (ACh) release in human neocortex slices

In slices of human neocortex, prelabelled with [H-3]-choline, the release o f [H-3]-acetylcholine reflects the evoked release of endogenous acetylcholi ne which was elicited by the same electrical stimulation paradigm. [H-3]-Ac etylcholine release was depressed by the delta-opioid receptor agonist D-Pe n(2)-D-Pen(5)-enkephalin. When the nerve endings were depolarized by elevat ing extracellular potassium the evoked [H-3]acetylcholine release was simil arly depressed by D-Pen(2)-D-Pen(5)-enkephalin in the absence, but not in t he presence, of tetrodotoxin which blocks action potential propagation, The refore, the delta-opioid receptor inhibiting [H-3]-acetylcholine release sh ould not be located to cholinergic nerve terminals, but rather to interneur ons. The somatostatin(2) receptor partial agonist octreotide pe, se did not influence action potential-evoked [H-3]-acetylcholine release, but prevent ed the inhibition of release of [H-3]-acetylcholine by D-Pen(2)-D-Pen(5)-en kephalin. Similarly, the delta(1)-opioid receptor antagonist 7-benzylidenen altrexon per se did not influence [H-3]-acetylcholine release, but prevente d of the inhibition of release by D-Pen(2)-D-Pen(5)-enkephalin. From the pr esent findings we conclude: (1) The evoked release of [H-3]-acetylcholine f rom human neocortex slices reflects the release of endogenous acetylcholine . (2) It is inhibited in an indirect manner by opioid receptors of the delt a(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 somatostatin(2) receptors, (C) 1999 ISDN. Published by Elsevie r Science Ltd. All rights reserved.