δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.

Pain relief is the principal action of opioids. Somatostatin a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that and δ-Opioid receptor (δOR) exist in a heteromeric complex and function in synergistic manner. duanyu1942R4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of duanyu1942R4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of and co-activation of duanyu1942R4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of Inhibition of cAMP/duanyu1529 and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between duanyu1942R4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.

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