OpenLB
Open Library of Bioscience
Advanced Search
British journal of pharmacology
Feb, 2006;147 (4): 360-70.

Agonist activity of naloxone benzoylhydrazone at recombinant and native opioid receptors.

Maria C Olianas, Danilo Concas, Pierluigi Onali
Author Information
  1. Maria C Olianas: Section of Biochemical Pharmacology, Department of Neuroscience, University of Cagliari, Monserrato, Cagliari, Italy.
PMID: 16402046 DOI: 10.1038/sj.bjp.0706601

Abstract

1. In the present study, we examined the pharmacological activity of the putative kappa3-opioid receptor agonist naloxone benzoylhydrazone (NalBzoH) at recombinant human opioid receptors individually expressed in Chinese hamster ovary (CHO) cells and native opioid receptors present in rat striatum. 2. At the mu-opioid receptor (MOR), NalBzoH stimulated guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding (pEC50=8.59) and inhibited cyclic AMP accumulation (pEC50=8.74) with maximal effects (Emax) corresponding to 55 and 65% of those obtained with the MOR agonist DAMGO, respectively. The MOR antagonist CTAP blocked the stimulatory effects of NalBzoH and DAMGO with similar potencies. 3. At the kappa-opioid receptor (KOR), NalBzoH stimulated [35S]GTPgammaS binding (pEC50=9.70) and inhibited cyclic AMP formation (pEC50=9.45) as effectively as the selective KOR agonist (-)-U-50,488. The NalBzoH effect was blocked by the KOR antagonist nor-binaltorphimine (nor-BNI) (pKi=10.30). 4. In CHO cells expressing the delta-opioid receptor (DOR), NalBzoH increased [35S]GTPgammaS binding (pEC50=8.49) and inhibited cyclic AMP formation (pEC50=8.61) almost as effectively as the DOR agonist DPDPE. Naltrindole (NTI), a selective DOR antagonist, completely blocked the response to NalBzoH (pKi of 10.40). 5. In CHO cells expressing the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), NalBzoH failed to exert agonist effects and antagonized the agonist-induced receptor activation. 6. When compared to other opioid receptor ligands, NalBzoH showed an efficacy that was lower than that of morphine at MOR, but higher at KOR and DOR. 7. In rat striatum, NalBzoH enhanced [35S]GTPgammaS binding and inhibited adenylyl cyclase activity. These effects were antagonized by either CTAP, nor-BNI or NTI, each antagonist blocking a fraction of the NalBzoH response. 8. These data demonstrate that NalBzoH displays agonist activity at MOR, DOR and KOR expressed either in a heterologous cell system or in a native environment.

References

  1. Behav Pharmacol. 1992 Apr;3(2):133-141 [PMID: 11224111]
  2. Neurosci Lett. 2001 Feb 23;299(3):173-6 [PMID: 11165763]
  3. Br J Pharmacol. 2003 Sep;140(1):61-70 [PMID: 12967935]
  4. J Neurosci. 1997 Nov 15;17(22):8721-8 [PMID: 9348341]
  5. Br J Pharmacol. 2002 Dec;137(8):1355-61 [PMID: 12466246]
  6. Mol Pharmacol. 1995 Jun;47(6):1180-8 [PMID: 7603458]
  7. J Med Chem. 1986 Nov;29(11):2370-5 [PMID: 2878079]
  8. Trends Neurosci. 1998 May;21(5):215-21 [PMID: 9610886]
  9. FEBS Lett. 1996 Oct 21;395(2-3):207-10 [PMID: 8898097]
  10. Brain Res. 1999 Nov 27;848(1-2):167-73 [PMID: 10612708]
  11. J Pharmacol Exp Ther. 1994 Sep;270(3):1246-55 [PMID: 7932177]
  12. Neuropharmacology. 2005 Feb;48(2):228-35 [PMID: 15695161]
  13. Nature. 1995 Oct 12;377(6549):532-5 [PMID: 7566152]
  14. J Neurochem. 1995 Jul;65(1):170-5 [PMID: 7790858]
  15. J Pharmacol Exp Ther. 1989 Nov;251(2):469-76 [PMID: 2553921]
  16. Mol Pharmacol. 1991 Mar;39(3):290-8 [PMID: 1848652]
  17. Science. 1995 Nov 3;270(5237):792-4 [PMID: 7481766]
  18. Eur J Pharmacol. 1992 May 12;226(1):15-20 [PMID: 1327838]
  19. Eur J Pharmacol. 1995 Apr 24;277(2-3):257-63 [PMID: 7493617]
  20. J Biol Chem. 1998 Jul 17;273(29):18047-51 [PMID: 9660760]
  21. Biochem Pharmacol. 1973 Dec 1;22(23):3099-108 [PMID: 4202581]
  22. Eur J Pharmacol. 1999 Jul 2;376(1-2):159-67 [PMID: 10440101]
  23. Br J Pharmacol. 2003 Mar;138(6):1049-58 [PMID: 12684260]
  24. Brain Res. 1997 Jan 2;744(1):41-6 [PMID: 9030411]
  25. Trends Neurosci. 1995 Jan;18(1):22-9 [PMID: 7535487]
  26. Anal Biochem. 1974 Apr;58(2):541-8 [PMID: 4827395]
  27. Anal Biochem. 1980 Sep 1;107(1):220-39 [PMID: 6254391]
  28. J Pharmacol Exp Ther. 1998 May;285(2):496-505 [PMID: 9580589]
  29. Mol Pharmacol. 1985 Nov;28(5):410-21 [PMID: 4058422]
  30. J Pharmacol Exp Ther. 1989 Nov;251(2):461-8 [PMID: 2553920]
  31. Synapse. 1996 Oct;24(2):193-201 [PMID: 8890461]
  32. Br J Pharmacol. 2004 Nov;143(5):638-48 [PMID: 15451772]
  33. Pharmacol Rev. 2001 Sep;53(3):381-415 [PMID: 11546835]
  34. Eur J Pharmacol. 1998 Apr 3;346(1):111-4 [PMID: 9617760]
  35. Mol Pharmacol. 1989 Jan;35(1):67-74 [PMID: 2536470]
  36. Anal Biochem. 1976 May 7;72:248-54 [PMID: 942051]
  37. Peptides. 1998;19(4):749-53 [PMID: 9622031]
  38. J Pharmacol Exp Ther. 1990 Nov;255(2):769-74 [PMID: 2173757]
  39. Naunyn Schmiedebergs Arch Pharmacol. 2001 Jun;363(6):583-9 [PMID: 11414652]
  40. J Pharmacol Exp Ther. 1996 Sep;278(3):1121-7 [PMID: 8819494]
  41. Eur J Pharmacol. 2000 Feb 18;389(2-3):107-14 [PMID: 10688973]
  42. Peptides. 2000 Jul;21(7):935-47 [PMID: 10998527]
  43. J Pharmacol Exp Ther. 1998 Jul;286(1):376-81 [PMID: 9655882]
  44. J Pharmacol Exp Ther. 1972 May;181(2):339-45 [PMID: 5063989]
  45. Can J Physiol Pharmacol. 2002 May;80(5):407-12 [PMID: 12056546]

MeSH Term

Adenylyl Cyclase Inhibitors
Adenylyl Cyclases
Animals
Binding, Competitive
CHO Cells
Cell Culture Techniques
Cell Extracts
Cell Membrane
Corpus Striatum
Cricetinae
Cyclic AMP
Dose-Response Relationship, Drug
Guanosine 5'-O-(3-Thiotriphosphate)
Humans
Male
Naloxone
Narcotic Antagonists
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptors, Opioid
Receptors, Opioid, kappa
Recombinant Proteins
Sulfur Radioisotopes

Chemicals

Adenylyl Cyclase Inhibitors
Cell Extracts
Narcotic Antagonists
Receptors, Opioid
Receptors, Opioid, kappa
Recombinant Proteins
Sulfur Radioisotopes
naloxone benzoylhydrazone
Naloxone
Guanosine 5'-O-(3-Thiotriphosphate)
Cyclic AMP
Adenylyl Cyclases
Comparative Study Journal Article

Word Cloud

Similar Articles

Cited By