μ-, δ- and κ-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate

Abstract

We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux from superfused rat brain slices. The differential inhibitory effects of these agonists on the evoked neurotransmitter release indicate that the opioid receptors mediating presynaptic inhibition of [3H]noradrenaline (NA, cortex), [14C]acetylcholine (ACh, striatum) and [3H]DA (striatum) release represent mu, delta and kappa receptors, respectively. In agreement with this classification, preincubation (60 min) of the slices with the delta-opioid receptor-selective irreversible ligand, fentanyl isothiocyanate (FIT, 0.01-1 microM), antagonized the inhibitory effects of DADLE and DPDPE on striatal [14C]ACh release only. On the other hand, the D-1 DA receptor-stimulated cyclic AMP efflux from striatal slices appeared to be inhibited by activation of mu as well as of delta receptors. In this case, the reversible mu antagonist, naloxone (0.1 microM), fully antagonized the inhibitory effect of the mu agonist, DAGO, without changing the effect of the delta agonist DPDPE but was ineffective as an antagonist in slices pretreated with FIT (1 microM). The inhibitory effect of DAGO on the electrically evoked [3H]NA release was antagonized by naloxone whether the receptors were irreversibly blocked by FIT or not. These data not only further support the existence of independent presynaptic mu-, delta- and kappa-opioid receptors in rat brain but also evidence strongly that mu and delta receptors mediating the inhibition of DA-sensitive adenylate cyclase could share a common binding site (for naloxone and FIT) and, therefore, may represent constituents of a functional opioid receptor complex.

Improvement by dynorphin A (1–13) of galanin‐induced impairment of memory accompanied by blockade of reductions in acetylcholine release in rats

“…Mulder et al (1984) found that lower doses of dynorphin A (1-13) inhibited both the spontaneous efflux of tritium and the potassium-induced release of [3H]-dopamine from rat striatal slices, whereas the release of ['4C]-acetylcholine was not significantly affected. Similar effects were also reported with administration of the selective K-agonist, U 50,488H, at concentrations below 1 ,IM (Schoffelmeer et al, 1988). Previously, we reported that the dose of dynorphin A (1-13) tested in this study did not alter dopamine release in the striatum, whereas higher doses of this peptide (2.5 and 5 nmol per rat, i.c.v.)…”

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

“…Slices (0.3 ϫ 0.3 ϫ 1 mm) were prepared using a McIlwain tissue chopper. For each experiment, brain slices from six animals were pooled, then incubated with radiolabeled DA, NE, or 5-HT as described previously (Schoffelmeer et al, 1988). In short, slices were washed twice with 5 ml of Krebs-Ringer's bicarbonate medium containing the following (in mM): 121 NaCl, 1.…”

Long-Lasting Cognitive Deficits Resulting from Adolescent Nicotine Exposure in Rats

“…In replicate experiments, brain tissue was sliced (0.3 Â 0.3 Â 2 mm) and for each brain region the slices of two animals were pooled. Subsequently, brain slices were incubated and superfused as described before (Schoffelmeer et al, 1988). Briefly, slices were incubated for 15 min in Krebs-Ringer bicarbonate containing 5 mCi [ 3 H] dopamine (Radiochemical Centre, Amersham, Buckinghamshire, UK) in an atmosphere of 95% O 2 -5% CO 2 at 371C.…”