title: Modulation of mu, kappa and delta opioid receptors in the rat brain by isoflurane and enflurane.
abstract: This study was done to investigate whether inhalational anesthetics modulated the binding of specific ligands to opioid receptors in the brain of the rat. The effect of isoflurane and enflurane on the binding of specific ligands to various subtypes of opioid receptors in vitro was studied. Isoflurane inhibited the binding of [3H]naloxone to opioid receptors by 50% in the spinal cord, midbrain and cortex at 22, 49 and 50 mM, respectively. Enflurane was more potent than isoflurane in inhibiting the binding of [3H]naloxone. Scatchard analysis of the binding of [3H]naloxone, done in the presence of therapeutic level (5 mM) of isoflurane, suggested that it did not affect the KD (1.3 nM) but decreased the Bmax by 41% in the cortex. Isoflurane and enflurane, at large doses (30-50 mM), inhibited the binding of [3H]ethylketo-cyclazocine (EKC) to kappa receptors in midbrain, cortex and spinal cord. At a smaller dose (5 mM), they increased the binding of EKC in spinal cord. The binding of the analogs of enkephalin [3H]DSTLE(Tyr-D-Ser-Gly-Phe-Leu-Thr-enkephalin) to delta receptors and [3H]DAGO (Tyr-D-Ala-Gly-Methyl-Phe-Glyol-enkephalin) to mu receptors in the midbrain and cortex was inhibited by isoflurane at a significantly smaller concentration than the binding of [3H]naloxone, indicating that the binding of peptides was more susceptible to the inhibition by inhalational anesthetics than the binding of alkaloids, such as naloxone or EKC. These results suggest that the modulation of opioid receptors by inhalational anesthetics is a function of both the nature of the ligand and the tissue used for the receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Ohio State University, College of Medicine, Columbus 43210-1239.
authors.forename: G A
authors.initials: GA
authors.lastname: Tejwani
authors.forename: A K
authors.initials: AK
authors.lastname: Rattan
authors.forename: K P
authors.initials: KP
authors.lastname: Gudehithlu
authors.forename: J S
authors.initials: JS
authors.lastname: McDonald
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004737:Enflurane / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine / Q000378:metabolism; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D004737:Enflurane; D007530:Isoflurane