Opiate modulating properties of nociceptin/orphanin FQ.
The recently discovered peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOR share many structural similarities with the opioid peptides and their receptors. The anatomical distributions of N/OFQ and NOR are similar to those of opioid peptides and receptors. In addition, NOR and opiate receptors couple via the same G-proteins to similar effectors, such as Ca(2+) channels, K(+) channels, adenylyl cyclase, and several protein kinases. Thus, the behavioral effects of N/OFQ have been investigated in the context of known opiate effects, and a possible connection has been sought between the effects of these two homologous signaling systems. Originally characterized as a nociception-producing peptide, N/OFQ has now been shown to have diverse effects on nociception, as well as effects on many other behaviors. With regard to nociception, the peptide has been reported to produce hyperalgesia, reversal of opioid-mediated analgesia, analgesia, and allodynia. N/OFQ also has effects on other behaviors, such as locomotion, feeding, anxiety, spatial attention, reproductive behaviors, and opiate tolerance. The relationship between opiates and N/OFQ is strengthened by the fact that opiates also affect these behaviors. However, the exact nature of the relationship of N/OFQ with opiates-opiate-like versus antiopiate-remains controversial. This review will detail the diverse effects of N/OFQ and suggest that this peptide, like other putative antiopiate peptides, can be described as 'opiate modulating. '
Harrison
L M
LM
Department of Physiology and Pharmacology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Grandy
D K
DK
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D004361:Drug Tolerance; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D010147:Pain Measurement; D011494:Protein Kinases / Q000378:metabolism; D011957:Receptors, Opioid / Q000502:physiology; D019966:Substance-Related Disorders; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D015220:Calcium Channels; D006728:Hormones; D018377:Neurotransmitter Agents; D018847:Opioid Peptides; D011494:Protein Kinases; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human