Non-opioid actions of opioid peptides.
Beside the well known actions of opioid peptides on mu-, delta- and kappa-opioid receptors, increasing amount of pharmacological and biochemical evidence has recently been published about non-opioid actions of various opioid peptides. These effects are not abolished by naloxone treatments. Such non-opioid effects are observed both in nervous tissues and in the cellular elements of the immune system. Peptides exhibiting non-opioid effects include beta-endorphin, dynorphin A, nociceptin/OFQ, endomorphins, hemorphins and a number of Proenkephalin A derived peptides, such as Met-enkephalin, Met-enkephalin-Arg-Phe (MERF) and bovine adrenal medullary peptide (BAM22). Non-opioid actions are exerted through different neuronal receptors, e.g., dynorphin hyperalgesia through NMDA receptor, Met-enkephalin induced regulation of cell growth through zeta receptors, pain modulation by nociceptin through ORL-1 or NOP receptors, while BAM22 acts through sensory neuron specific G protein-coupled receptors (SNSR). We have investigated Met-enkephalin-Arg-Phe (MERF) and its analogues by the means of direct and indirect radioligand binding assays. It has been found that in addition to kappa(2) and delta-opioid receptors, MERF can act also through sigma(2)- or probably via FMRF-NH(2) receptors in rat cerebellum. A role of functionally assembling heterodimer receptors in mediating the non-conventional actions of these peptide ligands can not be excluded as well.
Wollemann
Mária
M
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, PO Box 521, H-6701 Szeged, Hungary. wollemann@nucleus.szbk.u-szeged.hu
Benyhe
Sándor
S
D000818:Animals; D004399:Dynorphins / Q000502:physiology; D004723:Endorphins / Q000502:physiology; D004744:Enkephalin, Methionine / Q000502:physiology; D006801:Humans; D018847:Opioid Peptides / Q000494:pharmacology* / Q000502:physiology; D001615:beta-Endorphin / Q000502:physiology; D000097629:Nociceptin
D004399:Dynorphins; D004723:Endorphins; D004744:Enkephalin, Methionine; D018847:Opioid Peptides; D001615:beta-Endorphin; D000097629:Nociceptin