Signals in the Activation of Opioid µ-Receptors by Loperamide to Enhance Glucose Uptake into Cultured C₂C₁₂ Cells

Abstract

In an attempt to understand the signal pathways of opioid µ-receptors for glucose metabolism, we used loperamide to investigate the glucose uptake into the myoblast C₂C₁₂ cells. Loperamide enhanced the uptake of radioactive deoxyglucose into C₂C₁₂ cells in a concentration-dependent manner that was abolished in cells pre-incubated with naloxone or naloxonazine at concentrations sufficient to block opioid µ-receptors. Pharmacological inhibition of phospholipase C (PLC) by U73122 resulted in a concentration-dependent decrease in loperamide-stimulated uptake of radioactive deoxyglucose into C₂C₁₂ cells. This inhibition of glucose uptake by U73122 was specific since the inactive congener, U73343, failed to modify loperamide-stimulated glucose uptake. Moreover, both chelerythrine and GF 109203X diminished the action of loperamide at concentrations sufficient to inhibit protein kinase C (PKC). The obtained data suggest that an activation of opioid µ-receptors in C₂C₁₂ cells by loperamide may increase glucose uptake via the PLC-PKC pathway.

Key words

C₂C₁₂ cells - Loperamide - Opioid µ-receptors - Phospholipase C - Protein kinase C

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