Opioid receptor-mediated inhibition of evoked catecholamine release from cultured neurons of rat ventral mesencephalon and locus coeruleus.
The effects of selective opioid agonists on the evoked release of [3H]dopamine and [3H]noradrenaline were studied in cultured dopaminergic neurons of the ventral mesencephalon (containing the substantia nigra and ventral tegmental area) and in cultured neurons of the noradrenergic locus coeruleus, respectively. The cultures were prepared from embryonic day 15 rat brains. After 9 days in culture, the calcium-dependent release of [3H]dopamine from dopaminergic substantia nigra/ventral tegmental area neurons induced by 23 mM k+ appeared to be inhibited exclusively by activation of kappa-opioid receptors, as [3H]dopamine release was inhibited selectively by the kappa agonists U69,593 and dynorphin-(1-13) (EC50 8 and 5 nM, respectively), and this inhibitory effect was antagonized by the kappa-selective antagonist nor-binaltorphimine (Ki 0.07 nM). In contrast, cultured noradrenergic locus coeruleus neurons appeared to contain release-inhibitory mu-opioid receptors only, as evoked [3H]noradrenaline release was inhibited selectively by the mu agonist [D-Ala2, MePhe4, Gly-ol5]enkephalin (EC50 45 nM), a response that was antagonized by the preferential mu antagonist naloxone (Ki = 0.7 nM). The delta-opioid receptor agonist [D-Ser2(O-butyl), Leu5]enkephalyl-Thr6 did not affect catecholamine release. Dopamine release from cultured ventral mesencephalic neurons, induced by 100 microM N-Methyl-D-Aspartate (NMDA), also appeared to be subject to kappa receptor-mediated inhibition, whereas NMDA-induced noradrenaline release from cultured locus coeruleus neurons was under the inhibitor control of mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Ronken
E
E
Department of Pharmacology, Free University, Medical Faculty, Amsterdam, Netherlands.
Van Muiswinkel
F L
FL
Mulder
A H
AH
Schoffelmeer
A N
AN
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D014316:Tritium
D002395:Catecholamines; D005971:Glutamates; D011957:Receptors, Opioid; D014316:Tritium; D018698:Glutamic Acid; D016202:N-Methylaspartate; D004298:Dopamine; D009638:Norepinephrine