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.
Smith
J A
JA
Department of Pharmacology, California College of Medicine, University of California, Irvine 92717.
Loughlin
S E
SE
Leslie
F M
FM
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