Interactions of Na+,K+-ATPase and co-expressed δ-opioid receptor

To investigate interference of δ-opioid receptor with the Na+,K+-ATPase in a simple model system, we used the Xenopus oocytes as an expression system. Our results indicate that expression of the δ-opioid receptor (DOR) results in reduction of endogenous sodium-pump activity. Stimulation of DOR by the DOR agonist [D-Pen2,5]-enkephalin (DPDPE) had no pronounced additional effect on pump activity. Qualitatively similar results were obtained in experiments with a variety of co-expressed exogenous sodium pumps. We suggest that reduced pump activity with DOR expression is brought about by an interaction of the pump with DOR. Direct interaction is also supported by co-immunoprecipitation, not only in the Xenopus oocytes but also in rat hippocampal neurons. The interaction may be responsible for altered agonist sensitivity of DOR; activation of the sodium pump led to an increase of the Km value for DOR activation by DPDPE from about 0.17 to 0.27 μM. In conclusion, pump activity not only affects neural activity directly but our results also suggest that pump activity is affected through functional interaction with DOR that will modulate pain sensation.