CYTOCHEMICAL LOCALIZATION 

 OF NEUROTROPIC DRUGS 



J. H. QUASTEL 



McGill-Montreal General Hospital Research Institute, 

 3619 University Street, Montréal, Canada 



It is possible to obtain some information on the cytochemical localization 

 of neurotropic drugs by studies of the effects of such substances on 

 the metabolism of whole cells, as represented by surviving tissue 

 slices, or of cellular préparations such as mitochondria. 



Changes of the K /Ca ratio in the médium bathing brain cortex 

 slices bring about large changes in the respiration of the brain and 

 of the rates of conversion of radioactive glucose into radioactive amino 

 acids. Such changes do not affect metabolism of brain homogenates or 

 préparations in which the cell membranes hâve been disorganized. Thus 

 the cationic stimulation of brain cortex metabolism in vitro is a pheno- 

 menon associated with events at the cell membrane. 



The présence of ethanol, higher aliphatic alcohols and tribromethanol 

 at low concentrations suppresses the cationic stimulation of brain 

 cortex slices, but thèse alcohols at the same concentrations hâve no 

 effect on brain mitochondrial respiration or on the mitochondrial P/0 

 ratio. Thèse results point to the association of the alcohols with com- 

 ponents in the brain cell membrane which exert rate limiting effects on 

 cell metabolism. 



Acetylcholine, which affects P'^ turnover in the phospholipids of 

 brain, also plays a rôle at the cell membrane, probably by affecting 

 membrane transport of sodium and potassium ions. Potassium ions act 

 in a manner similar to acetylcholine in stimulating P'^ turnover in the 

 phospholipids of the brain cell. 



Protoveratrine, well known for its excitation of neuromuscular and 

 nervous Systems, has -effects on the metabolism of the brain cell, 

 resembling that due to increase of the K /Ca ratio in the m.edium 

 bathing the cell. Its action may be satisfactorily interpreted as due 

 toan immobilization of, or compétition with, calcium ions at the membrane. 

 Cocaine antagonizes the action of protoveratrine in vitro and apparently 

 acts by diminution of the K /Ca by a change of membrane transport, or 

 by replacing the calcium ion at a membrane ireceptor. 



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