The Effect of Chronic Morphine Treatment on the Abundance of Cell Signaling Proteins in the Guinea Pig Longitudinal Muscle‐Myenteric Plexus

Abstract

Chronic exposure to morphine produces heterologous tolerance in the longitudinal muscle/myenteric plexus (LM/MP) of the guinea pig. A decrease in the α3 subunit of the sodium pump was suggested as one mechanism since it develops over a time course similar to the reduced function. However, a large number of cell signaling proteins have also been proposed as contributors to the adaptation process. We examined the abundance of several different proteins using quantitative western blot analysis in homogenates of LM/MP after chronic morphine exposure. We found no change in the abundance of the mu opioid receptor protein either 4 or 7 days after pellet implantation when the loss of function occurs and becomes maximal. We also found no change in the abundance of the α1 subunit isoform of the sodium pump, PKCε, beta actin or GAPDH at any time period from 1–14 days after exposure. In contrast, we observed an increase in the abundance of calcineurin, GRK2, and Giα2 and a decrease in the abundance of PKCγ and the alpha3 subunit isoform at 7 days after implantation. The lack of correlation of changes in protein abundance with functional changes suggests that the heterologous tolerance that develops after chronic morphine treatment may involve multiple cellular mechanisms including the modulation of cell excitability and normal physiology which result from changes in the abundance of proteins in several signaling pathways.