Heterodimerization and cross-desensitization between the μ-opioid receptor and the chemokine CCR5 receptor

摘要: Abstract Cross-desensitization between μ-opioid receptor agonists and CC chemokines was shown to occur in immune cells the central nervous system. However, these do not permit examination of potential mechanisms at cellular levels due low mixed populations receptors. In this study, we investigated possible interactions biochemical cross-desensitization chemokine CCR5 receptors coexpressed Chinese hamster ovary (CHO) cells. Hemagglutinin (HA)-tagged coimmunoprecipitated with FLAG (Asp–Tyr–Lys–Asp–Asp–Asp–Asp–Lys)-tagged expressing two receptors, but a mixture transfected one indicating that form heterodimers. Treatment agonist DAMGO ([ d -Ala2, N-Me-Phe4, Gly5-ol]-enkephalin), RANTES (Regulated on Activation, Normal T cell-Expressed -Secreted) (CCL5), or both, did affect level coimmunoprecipitation. (CCL5) induced chemotaxis CHO coexpressing both preincubation either profoundly inhibited caused by other. pretreatment enhanced phosphorylation reduced (CCL5)-promoted [35S]GTPγS binding. Conversely, slightly increased significantly DAMGO-induced These results indicate activation affected G protein coupling other, likely receptor. Heterodimerization may contribute observed cross-desensitization.