The delta-opioid receptor regulates activity of ryanodine receptors in the human neuroblastoma cell line SK-N-BE.
Recent studies have demonstrated that opioid agonists affect the cytosolic Ca2+ concentration ([Ca2+]i) either by regulating plasma membrane Ca(2+)-channel activity or by mobilizing intracellular Ca2+ stores. The present report documents the [Ca2+]i increase induced by opioid agonists in a human neuroblastoma cell line, SK-N-BE, expressing delta-opioid receptors. In the presence, as well as in the absence, of extracellular Ca2+, opioid agonists enhanced significantly [Ca2+]i, whereas carbachol, known to mobilize specifically inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores, acted only in the presence of extracellular Ca2+. The opioid-induced increase in [Ca2+]i was not affected by treatments modifying the trimeric Gl, Go, and Gs protein transduction mechanisms or the activity of adenylyl cyclase. The Ca(2+)-ATPase pump-inhibiting sesquiterpene lactone, thapsigargin, did not modify the opioid-induced [Ca2+]i response, whereas it abolished the effects of carbachol. The Ryana speciosa alkaloid, ryanodine, at concentrations known to block endoplasmic reticulum ryanodine receptors, decreased significantly the response to opioids without affecting the effects of carbachol. Thus, our results suggest that, in SK-N-BE cells, delta-opioid receptors mobilize Ca2+ from intracellular ryanodine-sensitive stores and the mechanism involved is independent of Gl/Go Gs proteins and protein kinase A activation.
Allouche
S
S
Laboratoire des Neurosciences, URA 1829 CNRS, Université de Caen, France.
Polastron
J
J
Jauzac
P
P
D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology; D009447:Neuroblastoma; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D009124:Muscle Proteins; D009294:Narcotics; D017465:Receptors, Opioid, delta; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D019204:GTP-Binding Proteins; D002118:Calcium