Opioid-modulating peptides: mechanisms of action.
Opioids are involved in the physiological control of numerous functions of the central nervous system, particularly nociception. It appears that some endogenous neuropeptides, called anti-opioids, participate in an homeostatic system tending to reduce the effects of opioids. Neuropeptide FF (NPFF) and cholecystokinin (CCK) possess these properties and, paradoxically, the opioid peptides nociceptin and dynorphin display some anti-opioid activity. All these peptides exhibit complex properties as they are able to both counteract and potentiate opioid activity, acting rather as modulators of opioid functions. The purpose of this review is to highlight that two different mechanisms are clearly involved in the control of opioid functions by opioid-modulating peptides: a circuitry-induced mechanism for nociceptin and dynorphin, and a cellular anti-opioid mechanism for NPFF and CCK. The knowledge of these mechanisms has potential therapeutic interest in the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.
Mollereau
Catherine
C
Institut de Pharmacologie et Biologie Structurale du CNRS (UMR 5089), 205 route de Narbonne, 31077 Toulouse CEDEX 04, France. Catherine.mollereau-manaute@ipbs.fr
Roumy
Michel
M
Zajac
Jean-Marie
JM
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology*; D002766:Cholecystokinin / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D002766:Cholecystokinin; D004399:Dynorphins; D009020:Morphine; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide