Opioid receptor-mediated control of acetylcholine release in human neocortex tissue

Abstract

The effects of various opioid receptor agonists and antagonists on evoked acetylcholine release were studied in slices of human neocortex prelabelled with [3H]-choline, superfused and depolarized electrically (2 rain, 3 Hz, 2 ms, 24 mA) or by K + (20 raM). The 6-opioid receptor agonist DPDPE and the K-opioid receptor agonist U50488 reduced the evoked [3H]-overflow (acetylcholine release) in a concentration-dependent fashion; the cLopioid receptor antagonist naltrindole and the the ~c-opioid receptor antagonist norbinaltorphimine, respectively, antagonized these effects. Application of the g-opioid receptor agonist DAGO also resulted in an inhibition of acetylcholine release; however, both 6-and tc-opioid receptor antagonists were able to block this effect. The g-opioid receptor agonists morphine and (+)-nortilidine had no effect. These results indicate that acetylcholine release in human neocortex is inhibited through ~-and K-opioid receptors, but not through g-opioid receptors.Acetylcholine release was significantly increased by the cLopioid receptor antagonist naltrindole in the presence of a mixture of peptidase inhibitors providing evidence for a cLopioid receptor-mediated inhibition of acetylcholine release by endogenous enkephalin.K+-evoked acetylcholine release in the presence of TTX was inhibited by U50488, but not by DPDPE, suggesting the presence of ~c-opioid receptors on cholinergic terminals and the localization of c~-receptors on cortical interneurons. Therefore, the potent effect of DPDPE on acetylcholine release is likely to be indirect, by modulation of intrinsic cortical neurons. These interneurons probably do T.J. Feuerstein ([5~) • O. Gleichauf -D. Peckys not use GABA as neurotransmitter since both GABAA and GABAB receptor agonists (muscimol and baclofen, respectively) were without effect on acetylcholine release.

Functional Pharmacology in Human Brain

“…Because a previous report (Feuerstein et al, 1996b) excludes the involvement of GABA receptors in the ␦-opioid inhibition of ACh release, the findings raise the possibility that ␦ 1 receptor activation selectively affects the release of the cotransmitter somatostatin, although the existence of some "pure" somatostatinergic neurons should not be excluded.…”

“…), very few reports deal with neuropeptide receptors in human CNS. Results from experiments with laboratory animals show that opioids can regulate neurotransmitter release, although with important species differences [see Feuerstein et al (1996b) and references therein]. It is therefore important to investigate the modulation of release by opioids in human brain and, in particular, to characterize the subtypes of opioid receptor involved.…”

“…It is therefore important to investigate the modulation of release by opioids in human brain and, in particular, to characterize the subtypes of opioid receptor involved. Feuerstein et al (1996b) enkephalin and by the -opioid receptor agonist U50488. These effects were prevented, respectively, by the ␦-opioid antagonist naltrindole and the -opioid antagonist norbinaltorphimine.…”

“…Interestingly, naltrindole augmented, on its own, the evoked release of ACh, suggesting activation of ␦-opioid receptors by endogenous opioid peptides. Feuerstein et al (1996b) also suggested a localization of ␦-and -opioid receptors, based on experiments in which the release of ACh was elicited by high-K ϩ in the presence of tetrodotoxin. Because the K ϩ -evoked ACh release was inhibited by U50488, but not by DPDPE, the authors proposed that -opioid receptors are presynaptic on cholinergic terminals, whereas ␦-receptors are on cortical 174 RAITERI interneurons.…”

Roles of .Mu.-Opioid Receptors in Development of Tolerance to Diisopropylfluorophosphate (Dfp)

“…Naloxone, an µ-opioid receptor antagonist, antagonized the inhibitory effect of fentanyl on acetylcholine release in the hippocampus (Sakai et al, 2002). However, it has been reported that activation of µ-opioid receptor causes enhancement of acetylcholine release in several brain areas such as the striatum (Green et al, 1976), cortex (Feuerstein et al, 1996), hippocampus (Imperato et al, 1996), and rostral ventrolateral medulla (Taguchi et al, 1999). For example, morphine increased levels of acetylcholine in mouse striatum in a dose-dependent manner.…”