The effects of some porphyrinogenic drugs on the brain cholinergic system.
In central nervous system, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyse acetylcholine. Diminished cholinesterase activity is known to alter several mental and psychomotor functions. The symptoms of cholinergic crisis and those observed during acute attacks of acute intermittent porphyria are very similar. The aim of this study was to investigate if there could be a link between the action of some porphyrinogenic drugs on brain and the alteration of the cholinergic system. To this end, AChE and BuChE activities were assayed in whole and different brain areas. Muscarinic acetylcholine receptor (mAChR) levels were also measured. Results obtained indicate that the porphyrinogenic drugs tested affect central cholinergic transmission. Quantification of mAChR gave quite different levels depending on the xenobiotic. Veronal administration inhibited 50% BuChE activity in whole brain, cortex and hippocampus; concomitantly cortex mAChR was 30% reduced. Acute and chronic isoflurane anaesthesia diminished BuChE activity by 70-90% in whole brain instead cerebellum and hippocampus mAChR levels were only altered by chronic enflurane anaesthesia. Differential inhibition of cholinesterases in the brain regions and their consequent effects may be of importance to the knowledge of the mechanisms of neurotoxicity of porphyrinogenic drugs.
Rodriguez
Jorge Andres
JA
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP-CONICET), University of Buenos Aires, Argentine.
Buzaleh
Ana Maria
AM
Fossati
Mariana
M
Azcurra
Julio
J
Batlle
Alcira Maria  Del Carmen
AM
D000624:5-Aminolevulinate Synthetase / Q000187:drug effects; D000110:Acetylcholinesterase / Q000032:analysis / Q000187:drug effects; D000818:Animals; D001462:Barbital / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000032:analysis / Q000187:drug effects; D002802:Cholinesterases / Q000032:analysis / Q000187:drug effects*; D004737:Enflurane / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D006118:Griseofulvin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology; D011164:Porphyrias / Q000139:chemically induced / Q000150:complications*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects; D013217:Starvation / Q000378:metabolism
D011976:Receptors, Muscarinic; D006118:Griseofulvin; D000431:Ethanol; D001462:Barbital; D004737:Enflurane; D000624:5-Aminolevulinate Synthetase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases