Opioid Receptor Independent Effects of Opioid Peptides

Almost immediately after the discovery of opioid peptides and opioid receptors (ORs), reports were published that some effects of opioid peptides are independent of the activation of ORs. It was demonstrated that Des-Tyr1-fragments of opioid peptides did not interact with ORs but can exert different effects both in vivo and in vivo. They modify the functional state of the brain, the heart, the trachea, the aorta, arteries, natural killers, neutrophils, lymphocytes, and adrenal glands. It is quite obvious that non-ORs of Des-Tyr1-enkephalins, Des-Tyr1-dynorphins A, β-endorphin (2- 17), and β-endorphin (12-19) can be different. The physiological role of non-ORs of opioid peptides remains unknown because non-OR antagonists have not yet been found. It is unclear which Gproteins are coupled to non-ORs. It is unknown which intracellular messengers are involved in the effects of the activation of non-ORs by opioid peptides.