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. 1987 Jul;91(3):523–530. doi: 10.1111/j.1476-5381.1987.tb11245.x

Bremazocine differentially antagonizes responses to selective mu and delta opioid receptor agonists in rat hippocampus.

T V Dunwiddie, K J Johnson, W R Proctor
PMCID: PMC1853559  PMID: 3038241

Abstract

The effects of mu, delta and kappa opioid receptor agonists were examined on evoked field potentials in brain slices prepared from rat hippocampus. The effects of the mu-selective opioid peptide [D-Ala2, NMe-Phe4, Met(O)5ol]enkephalin (FK 33-824) and the delta-selective peptide [D-Pen2, D-Pen5]enkephalin (DPDPE) were qualitatively and quantitatively similar. Both increased the amplitude of evoked population spike responses when perfused in low nanomolar concentrations in a fashion consistent with what has been previously reported for other opiate agonists such as morphine. The kappa-selective agonists bremazocine and U-50, 488H were without effect upon evoked responses at concentrations as high as 10 microM. Bremazocine, but not U-50, 488H, proved to be an extremely potent antagonist of responses to both mu- and delta- selective agonists. Moreover, bremazocine was considerably more potent in antagonizing responses to FK 33-824 than DPDPE, which supports the hypothesis that FK 33-824 and DPDPE act via different receptors. Thus, although bremazocine is an agonist at kappa receptors, it appears to act as an antagonist at other opioid receptor sites.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bostock E., Dingledine R., Xu G., Chang K. J. Mu opioid receptors participate in the excitatory effect of opiates in the hippocampal slice. J Pharmacol Exp Ther. 1984 Dec;231(3):512–517. [PubMed] [Google Scholar]
  2. Brookes A., Bradley P. B. The effects of kappa opioid agonists in the rat hippocampal slice. Neuropeptides. 1984 Dec;5(1-3):261–264. doi: 10.1016/0143-4179(84)90077-5. [DOI] [PubMed] [Google Scholar]
  3. Chang K. J., Cooper B. R., Hazum E., Cuatrecasas P. Multiple opiate receptors: different regional distribution in the brain and differential binding of opiates and opioid peptides. Mol Pharmacol. 1979 Jul;16(1):91–104. [PubMed] [Google Scholar]
  4. Chang K. J., Cuatrecasas P. Multiple opiate receptors. Enkephalins and morphine bind to receptors of different specificity. J Biol Chem. 1979 Apr 25;254(8):2610–2618. [PubMed] [Google Scholar]
  5. Dingledine R. Possible mechanisms of enkephalin action on hippocampal CA1 pyramidal neurons. J Neurosci. 1981 Sep;1(9):1022–1035. doi: 10.1523/JNEUROSCI.01-09-01022.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dingledine R., Valentino R. J., Bostock E., King M. E., Chang K. J. Down-regulation of delta but not mu opioid receptors in the hippocampal slice associated with loss of physiological response. Life Sci. 1983;33 (Suppl 1):333–336. doi: 10.1016/0024-3205(83)90510-6. [DOI] [PubMed] [Google Scholar]
  7. Dunwiddie T. V., Fredholm B. B. Adenosine receptors mediating inhibitory electrophysiological responses in rat hippocampus are different from receptors mediating cyclic AMP accumulation. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jul;326(4):294–301. doi: 10.1007/BF00501433. [DOI] [PubMed] [Google Scholar]
  8. Dunwiddie T. V., Perez-Reyes E., Rice K. C., Palmer M. R. Stereoselectivity of opiate antagonists in rat hippocampus and neocortex: responses to (+) and (-) isomers of naloxone. Neuroscience. 1982 Jul;7(7):1691–1702. doi: 10.1016/0306-4522(82)90027-6. [DOI] [PubMed] [Google Scholar]
  9. Dunwiddie T., Lynch G. Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency. J Physiol. 1978 Mar;276:353–367. doi: 10.1113/jphysiol.1978.sp012239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunwiddie T., Mueller A., Palmer M., Stewart J., Hoffer B. Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. I. Effects on pyramidal cell activity. Brain Res. 1980 Feb 24;184(2):311–330. doi: 10.1016/0006-8993(80)90801-x. [DOI] [PubMed] [Google Scholar]
  11. Gillan M. G., Kosterlitz H. W., Magnan J. Unexpected antagonism in the rat vas deferens by benzomorphans which are agonists in other pharmacological tests. Br J Pharmacol. 1981 Jan;72(1):13–15. doi: 10.1111/j.1476-5381.1981.tb09098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gähwiler B. H., Maurer R. Involvement of mu-receptors in the opioid-induced generation of bursting discharges in hippocampal pyramidal cells. Regul Pept. 1981 May;2(2):91–96. doi: 10.1016/0167-0115(81)90003-3. [DOI] [PubMed] [Google Scholar]
  13. Kosterlitz H. W., Paterson S. J. Characterization of opioid receptors in nervous tissue. Proc R Soc Lond B Biol Sci. 1980 Oct 29;210(1178):113–122. doi: 10.1098/rspb.1980.0122. [DOI] [PubMed] [Google Scholar]
  14. Kosterlitz H. W. The Wellcome Foundation lecture, 1982. Opioid peptides and their receptors. Proc R Soc Lond B Biol Sci. 1985 Jul 22;225(1238):27–40. doi: 10.1098/rspb.1985.0048. [DOI] [PubMed] [Google Scholar]
  15. Lahti R. A., VonVoigtlander P. F., Barsuhn C. Properties of a selective kappa agonist, U-50,488H. Life Sci. 1982 Nov 15;31(20-21):2257–2260. doi: 10.1016/0024-3205(82)90132-1. [DOI] [PubMed] [Google Scholar]
  16. Lee H. K., Dunwiddie T., Hoffer B. Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. II. Effects on interneuron excitability. Brain Res. 1980 Feb 24;184(2):331–342. doi: 10.1016/0006-8993(80)90802-1. [DOI] [PubMed] [Google Scholar]
  17. Mosberg H. I., Hurst R., Hruby V. J., Gee K., Yamamura H. I., Galligan J. J., Burks T. F. Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5871–5874. doi: 10.1073/pnas.80.19.5871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nicoll R. A., Alger B. E., Jahr C. E. Enkephalin blocks inhibitory pathways in the vertebrate CNS. Nature. 1980 Sep 4;287(5777):22–25. doi: 10.1038/287022a0. [DOI] [PubMed] [Google Scholar]
  19. North R. A. Receptors on individual neurones. Neuroscience. 1986 Apr;17(4):899–907. doi: 10.1016/0306-4522(86)90070-9. [DOI] [PubMed] [Google Scholar]
  20. Robinson J. H., Deadwyler S. A. Morphine excitation: effects on field potentials recorded in the in vitro hippocampal slice. Neuropharmacology. 1980 Jun;19(6):507–514. doi: 10.1016/0028-3908(80)90019-2. [DOI] [PubMed] [Google Scholar]
  21. Roemer D., Buescher H. H., Hill R. C., Pless J., Bauer W., Cardinaux F., Closse A., Hauser D., Huguenin R. A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity. Nature. 1977 Aug 11;268(5620):547–549. doi: 10.1038/268547a0. [DOI] [PubMed] [Google Scholar]
  22. Valentino R. J., Dingledine R. Pharmacological characterization of opioid effects in the rat hippocampal slice. J Pharmacol Exp Ther. 1982 Nov;223(2):502–509. [PubMed] [Google Scholar]
  23. Vidal C., Maier R., Zieglgänsberger W. Effects of dynorphin A (1-17), dynorphin A (1-13) and D-ala2-D-leu5-enkephalin on the excitability of pyramidal cells in CA1 and CA2 of the rat hippocampus in vitro. Neuropeptides. 1984 Dec;5(1-3):237–240. doi: 10.1016/0143-4179(84)90071-4. [DOI] [PubMed] [Google Scholar]
  24. Von Voigtlander P. F., Lewis R. A. U-50,488, a selective kappa opioid agonist: comparison to other reputed kappa agonists. Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(4-6):467–470. doi: 10.1016/s0278-5846(82)80130-9. [DOI] [PubMed] [Google Scholar]
  25. Werz M. A., Macdonald R. L. Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials. J Pharmacol Exp Ther. 1983 Nov;227(2):394–402. [PubMed] [Google Scholar]
  26. Williams J. T., North R. A. Opiate-receptor interactions on single locus coeruleus neurones. Mol Pharmacol. 1984 Nov;26(3):489–497. [PubMed] [Google Scholar]
  27. Williams J. T., Zieglgänsberger W. Neurons in the frontal cortex of the rat carry multiple opiate receptors. Brain Res. 1981 Dec 7;226(1-2):304–308. doi: 10.1016/0006-8993(81)91103-3. [DOI] [PubMed] [Google Scholar]
  28. Yasuda R. P., Dunwiddie T. V., Zahniser N. R. The acute effects of 6-hydroxydopamine treatment on noradrenergic function in the rat hippocampus in vitro. Brain Res. 1986 Mar 5;367(1-2):121–127. doi: 10.1016/0006-8993(86)91585-4. [DOI] [PubMed] [Google Scholar]
  29. Zieglgänsberger W., French E. D., Siggins G. R., Bloom F. E. Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science. 1979 Jul 27;205(4404):415–417. doi: 10.1126/science.451610. [DOI] [PubMed] [Google Scholar]

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