Nociceptin, endomorphin-1 and-2 do not interact with invertebrate immune and neural mu(3) opiate receptor

AIM: To determine if endomorphin-1, -2 and nociceptin (orphanin FQ) bind to the mu(3) opiate receptor subtype or release nitric oxide as mu(3) selecti ve ligands do. METHODS: These opioid peptides were examined for their abili ty to displace [H-3]dihydromorphine (DHM) binding from the invertebrate (im munocytes and pedal ganglia) mu(3) opiate receptor in membrane homogenates. The ligands were also tested for their ability to release nitric oxide fro m the same intact tissues utilizing an amperometric probe that measures nit ric oxide in real-time. RESULTS: Endomorphin-1, -2 and nociceptin do not di splace [H-3]DHM binding from immunocyte or pedal ganglia membrane homogenat es nor do they release nitric oxide from these tissues. CONCLUSION: Since t hese newly discovered opioid peptides do not interact with the mu(3) Opiate receptor subtype, endogenous morphine's significance is enhanced because i t appears to be the only naturally occurring opiate ligand for the receptor . Furthermore, since this study involves invertebrate tissues, this signal system had to evolve early during evolution.