In vivo and in vitro evidence of a negative functional interaction between morphine and somatostatin

A functional interaction between opioids (OP) and somatostatin (SS) has been described for some physiological functions. Interestingly, it has been reported that patients undergoing antineoplastic somatostatin regimens show a decreased morphine (MP)-induced analgesia. By in vivo experiments we actually show that SS (2.5 g/kg) causes a significant decrease of the MP-induced analgesia in rat. Moreover, using SH-SY5Y cells (which express both opioids and SS receptors), we found that SS does not compete on MP binding to OP receptors, but induces a decrease of the effectiveness of MP to inhibit cAMP accumulation; chronic treatment with SS also induces tolerance to the MP-induced cAMP inhibition. These results confirm the existence of a negative functional cross talk between MP and SS at a single cell level, possibly through an heterologous receptor desensitization.