Nonopioid receptor-mediated effects of U-50,488H on [Ca(2+)]i and extracellular dopamine in PC12 cells.
The present studies were carried out to determine the effects of a kappa-opioid receptor agonist on cytosolic Ca(2+) concentration, [Ca(2+)](i), and extracellular dopamine in undifferentiated PC12 cells. The kappa-opioid receptor agonist U-50,488H caused concentration-dependent increases in [Ca(2+)](i) and extracellular dopamine. Neither effect was blocked by the selective kappa-opioid receptor antagonist nor-binaltorphimine. Increases in extracellular dopamine content and [Ca(2+)](i) caused by U-50,488H were correlated positively in the presence of extracellular Ca(2+); however, reduction of extracellular Ca(2+) abolished the increase in [Ca(2+)](i), but not that in dopamine. The latter observation suggests that stimulation of exocytotic release is not the primary mechanism involved in the increase in extracellular dopamine caused by U-50,488H. Effects on dopamine synthesis or catabolism also seem unlikely because the enhancement of extracellular dopamine occurred rapidly, and the amount of a major metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), was not affected. In any event, neither the increase in [Ca(2+)](i) nor the increase in extracellular dopamine caused by U-50,488H is mediated by the kappa-opioid receptor.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Nuannoi
N
Chudapongse
Seong-Youl
SY
Kim
Kenroh
K
Sasaki
Robert E
RE
Kramer
Ing K
IK
Ho
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007424:Intracellular Fluid / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists
D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002118:Calcium; D004298:Dopamine