Alterations of Phospholipid Metabolism in Rat Cerebral Cortex Mince Induced by Cationic Amphiphilic Drugs

Anuradha S. Pappu, George Hauser

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Abstract Cationic amphiphilic drugs (CADs) of varied clinical use were screened to determine their capacity to alter the pattern of labeling with 32Pj of cerebral cortex mince phospholipids. The altered phospholipid labeling patterns were qualitatively similar, the prominent features being reduced incorporation into phosphatidylcholine and increased incorporation into phosphatidic acid. Relative potencies were: (±)‐propranolol > chlorpromazine = 4,4′‐bis(diethylaminoethoxy) α,β‐diethyldiphenylethane > desipramine > di‐bucaine > pimozide > oxymetazoline = fenfluramine = haloperidol = chloroquine > amphetamine = no drug added. Propranolol was used to study the action of CADs further. Its effect was time‐ and dose‐dependent, but in contrast with pineal gland, no label appeared in phosphatidyl‐CMP (CDP‐diacylglycerol), nor did dialysis of the mince to reduce diffusible substrates or exogenous addition of substrates cause appearance of liponucleotide. Thus lack of diffusible precursors is not responsible for CAD effects in vitro. Pulse‐chase experiments with 32P1 and [2‐3H]glycerol suggested that inhibition of phosphatidate phosphohydrolase may be partly responsible for the observed alterations in phospholipid labeling in the presence of CADs.

Original languageEnglish (US)
Pages (from-to)1006-1014
Number of pages9
JournalJournal of Neurochemistry
Volume37
Issue number4
DOIs
StatePublished - Oct 1981

Keywords

  • Cationic amphiphilic drugs
  • Cerebral cortex lipids
  • Phosphatidic acid
  • Phospholipid metabolism
  • Propranolol

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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