Relevance of phosphorylation state to opioid responsiveness in opiate naive and tolerant/dependent tissue
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Cited by (31)
Therapeutic Targeting of "DARPP-32". A Key Signaling Molecule in the Dopiminergic Pathway for the Treatment of Opiate Addiction
2009, International Review of NeurobiologyCitation Excerpt :Tolerance and physical dependence have been correlated with changes in the intracellular cAMP signal transduction cascade. Elements of the cascade found to be altered include G-proteins, adenylate cyclase, protein kinase A (PKA), and its target CREB (cAMP response element-binding) (Nestler et al., 1994; Wang and Gintzler, 1997; Wang et al., 1996). The activity of CREB is regulated by phosphorylation and opiates have been shown to alter phosphorylation of CREB protein.
The antinociceptive effect of morphine is reversed by okadaic acid in morphine-naive but not in morphine-tolerant mice
2007, Pharmacology Biochemistry and BehaviorPhosphorylation: A molecular switch in opioid tolerance
2006, Life SciencesChronic morphine-induced loss of the facilitative interaction between vasoactive intestinal polypeptide and δ-opioid: Involvement of protein kinase C and phospholipase Cβs
2004, Brain ResearchCitation Excerpt :These results indicate that the VIP–DPDPE multiplicative enhancement of spinal cAMP formation is subject to opioid tolerance, which is consistent with the previously observed ability of chronic systemic morphine to produce cross-tolerance with δ-opioid receptor-mediated antinociception [45]. In order to explore the involvement of PKC phosphorylation in the chronic morphine-induced loss of the VIP–DPDPE facilitative interaction, we assessed whether or not it could be mitigated by acute in vitro treatment with the highly selective PKC inhibitor chelerythrine [25] as previously utilized [41,42]. In in vivo chronic morphine-exposed spinal tissue that had been treated in vitro with chelerythrine, basal levels of cAMP were 8.48±0.76 pmol/mg protein, comparable to values obtained in the absence of opioid.
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Mildred Rivera is an Aaron Diamond Foundation Fellow.