Acute delta-opioid receptor activation induces CREB phosphorylation in NG108-15 cells

A growing body of evidence supports an important role of the transcription factor cAMP responsive element binding protein (CREB) in mediating opioid-i nduced changes in the cAMP pathway. Regulation of CREB and subsequent chang es in gene expression may underlie some long-term cellular adaptations asso ciated with the administration of opioid drugs. The effect of morphine on t he level of the transcription factor CREB, as well as CREB phosphorylation, was investigated in NG108-15 cells. Morphine and the delta-opioid receptor agonist [(D)-Pen(2,5)]enkephalin (DPDPE) produced a dose-dependent increas e in CREB phosphorylation. The effect was reversed by naloxone and naltrind ole, respectively. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-na phthalenesulfonamide hydrochloride (W-7), the protein kinase inhibitor stau rosporine, as well, as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydr ochloride (H-7), an inhibitor of protein kinase C and cAMP-dependent protei n kinase, but not N[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydro chloride (H-8), an inhibitor of cAMP- and cGMP-dependent protein kinase, bl ocked the opioid-induced CREB phosphorylation. The obtained results suggest that in the cells studied opioids affect, via the delta-opioid receptor, s timulatory intracellular mediator systems involving Ca2+/calmodulin and the protein kinase C pathway. (C) 2000 Elsevier Science B.V. All rights reserv ed.