Article ID Journal Published Year Pages File Type
2535726 European Journal of Pharmacology 2008 7 Pages PDF
Abstract

Voltage-gated L- and N-type calcium channels (VOCs) are implicated in the activity of morphine, but their contribution to the expression of opioid tolerance remains uncertain. L- and N-type VOCs are heteropentamers of α1, α2δ, β, and γ subunits. The α1 subunit forms both the ion pore and the binding site for ligands. The Cav1.2 and Cav1.3 are the neuronal dihydropyridine (DHP)-sensitive L-type channel subunit types. The Cav2.2 subunit is found in omega conotoxin GVIA-sensitive N-type calcium channels. Cav1.2 VOC gating properties are phosphorylation-dependent with many kinases implicated. We hypothesized that changes in channel subunit structure or phosphorylation state, induced by chronic opioid exposure, may in part explain changes in calcium regulation observed both in vivo and in vitro. Antibodies, specific for the Cav1.2, Cav1.3, and Cav2.2 subunits of VOCs were employed with Western immunoassays to access whether chronic morphine treatment had an effect on receptor protein levels. The L-type channel Cav1.3 protein, but not the Cav1.2 protein or phosphorylation state, significantly decreased upon chronic morphine treatment. The Cav2.2 subunit protein of the N-type channel of VOCs remained unchanged. The Cav1.3 subunit modification may represent one of many potential adaptive changes in tolerance to morphine-induced changes in intracellular calcium.

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