Microinjection of the Kappa Opioid Receptor Agonist U‐50448h Into the Medial Preoptic Area Increases Renal Sna and Decreases Sodium Excretion Without Significantly Impacting Cardiovascular Function

Afshar, Roxana; Franklin, Cynthia; Rangel, Yolanda; Toney, Glenn M.; Gottlieb, Helmut

doi:10.1096/fasebj.25.1_supplement.1079.20

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“…KOP agonists also produce effects on renal nerves, intact adrenal glands and the kidney 11,44–47 . Radioligand binding studies and in vitro kidney perfusion assays have shown the presence of KOP in the glomerulus of the nephron and the cortex of the kidney 16,48 .…”

Section: Discussionmentioning

confidence: 99%

“…KOP agonists also produce effects on renal nerves, intact adrenal glands and the kidney. 11,[44][45][46][47] Radioligand binding studies and in vitro kidney perfusion assays have shown the presence of KOP in the glomerulus of the nephron and the cortex of the kidney. Although KOP expression in rat kidneys is low compared with the brain, 49,50 perfusion of the KOP agonist bremazocine in the isolated rat kidney significantly increased the glomerular filtration rate, urine output and electrolyte excretion.…”

Section: Notementioning

confidence: 99%

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Effects of sex and hydration status on kappa opioid receptor‐mediated diuresis in rats

Lalji,

Bailey,

Husbands

et al. 2024

Basic Clin Pharma Tox

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Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress‐related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre‐clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1–10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water‐loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre‐administration. Water‐loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females.

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Section: Discussionmentioning

confidence: 99%