Abstract
We previously characterized multiple interactions between chemokine and opioid G protein-coupled receptors (GPCR), and we found both mu and delta-opioid receptors cross-desensitize CCR1, CCR2, CCR5, but not CXCR4. Here we report that the kappa-opioid receptor (KOR) is able to cross-desensitize CXCR4, and this phenomenon is bi-directional. Chemotactic responses by KOR activation are diminished with prior activation of CXCR4. Additionally, calcium mobilization assays show these cross-desensitization processes occur within seconds of receptor activation, and target receptor internalization is not responsible for desensitization between these receptors. These results have implications for several essential processes including neuronal and lymphocyte development, inflammatory responses, and pain/sensitivity.