Effect of ORG 34116, a corticosteroid receptor antagonist, on hippocampal Ca2(+) currents

H Karst*, ER de Kloet, M Joels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

ORG 34116, a substituted 11,21-bisarylsteroid compound, binds selectively and with high affinity to human and rat glucocorticoid receptors. At the level of the hypothalamus it attenuates the negative feedback action of corticosterone, suggesting that it acts as an antagonist. In the present study we examined the effect of in vitro and in vivo administered ORG 34116 on cell properties of higher brain areas, i.e. on Ca2+ current characteristics of CA1 hippocampal neurons recorded with whole cell techniques in hippocampal slices. We observed that in vitro applied ORG 34116 antagonized corticosterone induced effects on Ca2+ currents. Data observed after in vivo application of ORG 34116 corroborate these findings. The results furthermore suggest that pretreatment with the glucocorticoid receptor antagonist ORG 34116 also prevents the development of mineralocorticoid receptor mediated effects on Ca2+ currents. If ORG 34116 should indeed prove to be a corticosterone rather than glucocorticoid receptor selective antagonist, this drug may turn out to be an important tool in the treatment of stress-related disorders. (C) 1997 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalEuropean Journal of Pharmacology
Volume339
Issue number1
DOIs
Publication statusPublished - 19-Nov-1997
Externally publishedYes

Keywords

  • mineralocorticoid
  • glucocorticoid
  • hippocampal slice
  • patch clamp recording
  • GLUCOCORTICOID RECEPTOR
  • MINERALOCORTICOID RECEPTOR
  • NERVOUS-SYSTEM
  • BRAIN
  • NEURONS
  • CONDUCTANCES
  • CALCIUM

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