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

Title
Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal nor-binaltorphimine in monkeys
Authors
Ko M.C.H.Willmont K.J.Lee H.Flory G.S.Woods J.H.
Ewha Authors
이희승
SCOPUS Author ID
이희승scopus
Issue Date
2003
Journal Title
Brain Research
ISSN
0006-8993JCR Link
Citation
vol. 982, no. 1, pp. 38 - 44
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2003 Elsevier B.V. All rights reserved.
DOI
10.1016/S0006-8993(03)02938-X
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의과대학 > 의학과 > Journal papers
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