In vivo study on mechanism underlying increased pharmacological effects of phenobarbital in rats with glycerol-induced acute renal failure

Atsuyoshi Okada, Keiichiro Suzuki, Keisuke Hara, Moeko Kojina, Tetsuya Aiba

Research output: Contribution to journalArticle

Abstract

The mechanism underlying the increased pharmacological effects of phenobarbital in rats with glycerol-induced acute renal failure (ARF) was examined. In the experiments, a surgical cannula was inserted in the lateral ventricle of the rats for phenobarbital infusion, and the ARF induction was performed by intramuscular administration of 50% glycerol. The onset time of anesthesia by phenobarbital was determined with the tail flick method. In addition, cerebral microsomes were prepared from excised cerebral cortices of sham and ARF rats, and the cerebral expression of the γ-aminobutyric acid (GABA) A receptor and two cation-chloride transporters, KCC2 and NKCC1, was evaluated by Western blotting, as their functions are involved in the anesthetic effects of phenobarbital. When phenobarbital was infused in the ventricle, anesthesia was induced 2.2-times faster in ARF rats than in sham rats, and there was no detectable increase in the cerebral expression of the GABA A receptor in ARF rats. It was additionally noted that the cerebral expression of KCC2 decreased, whereas that of NKCC1 was unaltered in ARF rats. These findings indicated that the anesthetic effects of phenobarbital are potentiated in ARF rats, probably due to imbalanced cerebral expression of KCC2 and NKCC1, suggesting that altered cation-chloride handling in nerve cells is associated.

Original languageEnglish
Pages (from-to)501-506
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume42
Issue number3
DOIs
Publication statusPublished - Jan 1 2019

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Phenobarbital
Acute Kidney Injury
Glycerol
Pharmacology
GABA-A Receptors
Anesthetics
Cations
Chlorides
Anesthesia
Aminobutyrates
Lateral Ventricles
Microsomes
Cerebral Cortex
Tail
Western Blotting
Neurons

Keywords

  • Acute renal failure
  • Anesthesia
  • KCC2
  • NKCC1
  • Phenobarbital

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

In vivo study on mechanism underlying increased pharmacological effects of phenobarbital in rats with glycerol-induced acute renal failure. / Okada, Atsuyoshi; Suzuki, Keiichiro; Hara, Keisuke; Kojina, Moeko; Aiba, Tetsuya.

In: Biological and Pharmaceutical Bulletin, Vol. 42, No. 3, 01.01.2019, p. 501-506.

Research output: Contribution to journalArticle

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