Nociceptin, endomorphin-1 and-2 do not interact with invertebrate immune and neural μ3 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) selective ligands do. METHODS: These opioid peptides were examined for their ability to displace [H-3]dihydromorphine (DHM) binding from the invertebrate (immunocytes and pedal ganglia) mu(3) opiate receptor in membrane homogenates. The ligands were also tested for their ability to release nitric oxide from the same intact tissues utilizing an amperometric probe that measures nitric oxide in real-time. RESULTS: Endomorphin-1, -2 and nociceptin do not displace [H-3]DHM binding from immunocyte or pedal ganglia membrane homogenates nor do they release nitric oxide from these tissues. CONCLUSION: Since these newly discovered opioid peptides do not interact with the mu(3) Opiate receptor subtype, endogenous morphine's significance is enhanced because it 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.