Antinociceptive and gastrointestinal effects of opiates: an analysis of the nature of the involvement of mu and delta receptors of the central nervous system in morphine-tolerant and non-tolerant mice.
This study attempted to distinguish between mu (morphine) and delta [(D-Ala2-D-Leu5)-enkephalin; DADLE] receptors, with regard to both in vivo effects (analgesia and gastrointestinal motility) and the location of binding activity in the brain. Analgesia and motility are distinguishable both by dose (intracerebroventricular) and by ligand selectivity with mu ligands more potent for the former and delta for the latter. Tolerance and cross-tolerance are exhibited for both effects, with the relationships between mu and delta ligand potencies preserved. In vitro receptor binding revealed an affinity decrease for delta in medulla and an increase in medulla and diencephalon for mu receptors after tolerance development to morphine. The results indicate that the mu receptors in medulla and diencephalon mediate analgesia, while medullary delta receptors control motility.
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000502:physiology*; D004361:Drug Tolerance; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine