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Alterations of Phospholipid Metabolism in Rat Cerebral Cortex Mince Induced by Cationic Amphiphilic Drugs
Author(s) -
Pappu Anuradha S.,
Hauser George
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb04488.x
Subject(s) - chemistry , desipramine , phospholipid , phosphatidylcholine , pharmacology , phospholipidosis , phosphatidic acid , propranolol , chlorpromazine , haloperidol , biochemistry , endocrinology , medicine , membrane , dopamine , biology , antidepressant , hippocampus
Cationic amphiphilic drugs (CADs) of varied clinical use were screened to determine their capacity to alter the pattern of labeling with 32 Pj 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 32 P 1 and [2‐ 3 H]glycerol suggested that inhibition of phosphatidate phosphohydrolase may be partly responsible for the observed alterations in phospholipid labeling in the presence of CADs.