title: The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit.
abstract: Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012018:Reflex / Q000187:drug effects*
chemical_list: D004723:Endorphins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine