Abstract
BACKGROUND: The delta(delta)-opioid receptors belong to the G protein-coupled receptors and in vitro studies have shown that delta-opioid receptors undergo an internalization process in response to agonist stimulation. The immediate consequence is the disappearance of receptors from the plasma membrane. This adaptation process reveals the cell's capacity to desensitize after a strong agonist stimulus. This process, if it occurs in vivo, could contribute to the tolerance phenomenon observed after opiate treatment. To study the mechanisms underlying regulation of the delta-opioid receptors in vivo, the effects of an application of the drug dermenkephalin, a potent and selective agonist of the delta-opioid receptor, were analysed in the rat spinal cord. RESULTS: Using immunocytochemistry and electron microscopy, we observed in control rats that membrane labelling was strictly localized at the interface between two neurites. Fifteen minutes after dermenkephalin stimulation, the plasma membrane labelling was associated with invaginated areas. Thirty minutes after stimulation, labelled vesicles were found in the cytoplasm confirming the internalization process. CONCLUSIONS: The present findings support the view that delta-opioid receptors are internalized in response to prolonged exposure to dermenkephalin in vivo and confirm the presynaptic localization of delta-opioid receptors in the dorsal horn of the rat spinal cord.