Effects of a kappa-receptor agonist, U-50,488H, on the release of endogenous brain dopamine.
The potential interaction between kappa-opiate receptors and dopamine activity was examined in this study by monitoring the effect of U-50,488H on the release of endogenous dopamine from rat striatal slices in both the absence and presence of 10 microM nomifensine, a potent dopamine uptake inhibitor. Basal dopamine release was increased 10-fold in the presence of nomifensine, and the normally steady base line was observed to increase gradually under these conditions. U-50,488H, a potent kappa-agonist, enhanced the spontaneous release of dopamine, but only at relatively high concentrations (40.0 microM) and only in the absence of nomifensine. Likewise, nomifensine and U-50,488H (40.0 microM) each significantly inhibited the synaptosomal uptake of [3H]dopamine. As with basal release, nomifensine markedly enhanced the potassium-evoked release of dopamine, and this evoked release was significantly attenuated by U-50,488H (0.4 and 40.0 microM) in both the absence and presence of nomifensine. This opiate-mediated inhibition of evoked dopamine release was antagonized in a time-dependent manner by the putative kappa-antagonist, WIN 44,441-3, suggesting that striatal kappa-receptor activation modulates dopamine release.
Clow
D W
DW
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
Jhamandas
K
K
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D001392:Azocines; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D011188:Potassium; D004298:Dopamine; C035969:quadazocine