The stimulatory effect of opioids on cyclic AMP production in SK-N-SH cells is mediated by calcium ions.
The present study examines the stimulatory effect of opioids on adenosine 3':5'-cyclic monophosphate (cyclic AMP) production in the human neuroblastoma cell line SK-N-SH, and its dependence on calcium. We show that, in this culture, the mu-opioid selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin stimulates cyclic AMP production by 30% in a naloxone-reversible manner. This stimulation is completely dependent on calcium and involves the activation of calcium/calmodulin since it is abolished in the presence of EGTA, calcium channel blockers or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7). The results suggest that the activation of calcium/calmodulin dependent adenylyl cyclases by opioids in SK-N-SH cells is secondary to the induction of calcium influx and the consequent elevation of intracellular calcium level.
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Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D006801:Humans; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D004745:Enkephalins; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D013449:Sulfonamides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004533:Egtazic Acid; C017967:W 7; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium