kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic dissociated cell cultures.
The present study investigated the effect of opioids on [3H]dopamine release from mixed neuronal-glial cell cultures of embryonic rat ventral mesencephalon. Each of the major morphological types of dopaminergic cell was represented in these cultures. These cells exhibited specific uptake of [3H]dopamine, which was subsequently released, in a calcium-dependent manner, in response to a double pulse of elevated extracellular potassium. Spontaneous and potassium-evoked [3H]dopamine release was inhibited by kappa- but not mu- or delta-opioid agonists. The selective kappa 1 agonist (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-[7-(1-pyrollidinyl)-1-oxaspiro(4,5)- dec-8-yl]benzeneacetamide (U69593) produced a dose-dependent inhibition of dopamine release. The effect of U69593 was blocked by the nonselective opiate antagonist naloxone and the selective kappa opioid antagonist norbinaltorphimine. kappa-Opioid inhibition of potassium-evoked [3H]dopamine release was maintained in the presence of tetrodotoxin. These results suggest that functional kappa receptors, modulating dopamine release, are localized on the terminals of dopaminergic neurons.
Department of Pharmacology, California College of Medicine, University of California, Irvine 92717.
J A
JA
Smith
S E
SE
Loughlin
F M
FM
Leslie
D000818:Animals; D044482:Benzeneacetamides; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D044482:Benzeneacetamides; D004745:Enkephalins; D009294:Narcotics; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D013779:Tetrodotoxin; D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593; D011188:Potassium; D002118:Calcium; D004298:Dopamine