Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal nor-binaltorphimine in monkeys

M. C.H. Ko, K. J. Willmont, H. Lee, G. S. Flory, J. H. Woods

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Kappa opioid receptor (KOR) agonists such as U-50488H and bremazocine are analgesics and diuretics. In monkeys, the selective KOR antagonist, nor-binaltorphimine (nor-BNI), produces a long-lasting antagonism of the antinociceptive effects of U-50488H but not those of bremazocine, suggesting that KOR-mediated antinociception may occur through two distinct KORs. The aim of this study was to characterize the antagonist effect of nor-BNI against the diuretic effects of U-50488H and bremazocine in monkeys. Urine outputs were collected over 3 h subsequent to i.m. administration of KOR agonists. Both U-50488H (0.032-1 mg/kg) and bremazocine (0.00032-0.01 mg/kg) dose-dependently increased urine output and the diuretic effect reached a plateau at higher doses. The maximum effect of either U-50488H or bremazocine was approximately 15 ml/kg/3 h of urine. Pretreatment with intracisternal nor-BNI 0.32 mg significantly blocked both U-50488H (0.18 mg/kg)- and bremazocine (0.0032 mg/kg)-induced diuresis for 20 weeks. However, the same dose of nor-BNI 0.32 mg given subcutaneously was not effective. These results demonstrate that central KOR mediate KOR agonist-induced diuresis in monkeys. More important, this study provides functional evidence for a homogenous population of KOR underlying KOR-mediated diuresis and illustrates a unique pharmacological profile of nor-BNI-induced ultra-long KOR antagonism in vivo.

Original languageEnglish (US)
Pages (from-to)38-44
Number of pages7
JournalBrain Research
Volume982
Issue number1
DOIs
StatePublished - Aug 22 2003

Keywords

  • Cisterna magna
  • Diuresis
  • Kappa opioid receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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