Effects of acute and chronic barbiturate administration on synaptosomal calcium accumulation

M. G. Ondrusek, J. K. Belknap, S. W. Leslie

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Synaptosomes were isolated from four treatment groups of DBA/2J mice; Group I-Control; Group II-7 day tolerant (received dietary phenobarbital, 2.5 mg/g Purina Lab Chow for 7 days); Group III-20 hr withdrawn; and Group IV-7 day recovered (received dietary phenobarbital for 7 days followed by normal diet for 7 days). Pentobarbital (0.45 mM) added in vitro to synaptosomes from control mice significantly depressed (21.4%) potassium depolarized 45Ca++ accumulation but did not significantly alter nondepolarized 45Ca++ uptake or subsequent 45Ca++ efflux. Chronic administration of phenobarbital to mice in the tolerant and withdrawn conditions resulted in behavioral tolerance and subsequent withdrawal symptomatology, but neither KCl-induced 45Ca++ accumulation nor 45Ca++ efflux was significantly altered. In vitro addition of pentobarbital (0.45 mM) to synaptosomes from tolerant mice did not significantly depress KCl-induced 45Ca++ accumulation (8.1%) but did significantly depress KCl-induced 45Ca++ accumulation by synaptosomes from withdrawn mice (15.2%) and recovered mice (16.8%). These data suggest that barbiturates may depress calcium-mediated stimulus-secretion coupling events contributing to central nervous system depression. Further, functional tolerance after chronic barbiturate treatment may result from a membrane adaptation facilitating calcium-mediated secretory functions.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalMolecular pharmacology
Volume15
Issue number2
StatePublished - Dec 1 1979

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Ondrusek, M. G., Belknap, J. K., & Leslie, S. W. (1979). Effects of acute and chronic barbiturate administration on synaptosomal calcium accumulation. Molecular pharmacology, 15(2), 386-395.