Endogenous generation of cyanide in neuronal tissue: involvement of a peroxidase system.
In a study of the mechanism by which cyanide is produced in neural tissue, it was hypothesized that nerve cells generate cyanide in a manner similar to that in leukocytes. As in white blood cells, glycine addition enhanced cyanide production in rat pheochromocytoma cells. Because myeloperoxidase catalyses cyanide production in leukocytes, a selective myeloperoxidase inhibitor (aminobenzoic acid hydrazide) was tested and found to inhibit opiate agonist-induced cyanide production in pheochromocytoma cells and also in rat brain. In addition, hydrogen peroxide enhanced cyanide release in pheochromocytoma cells, further suggesting that the process is oxidative in nature. Sonicated rat pheochromocytoma cells did not generate cyanide in response to an agonist acting on surface receptors even though disrupted cells responded to glycine. The mitochondrial fraction from rat brain produced more cyanide in response to glycine than any other fraction. Thus glycine seems to act at an intracellular site to enhance cyanide production and the process seems to involve a peroxidase mechanism similar to that reported for white blood cells.
Gunasekar
P G
PG
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Borowitz
J L
JL
Turek
J J
JJ
Van Horn
D A
DA
Isom
G E
GE
D062365:Aminobenzoates / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002458:Cell Fractionation; D018679:Cholinergic Agonists / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D004091:Hydromorphone / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D016716:PC12 Cells; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D062365:Aminobenzoates; D000701:Analgesics, Opioid; D001386:Azides; D018679:Cholinergic Agonists; D003486:Cyanides; D009294:Narcotics; D016877:Oxidants; D009020:Morphine; D002217:Carbachol; D006861:Hydrogen Peroxide; D010544:Peroxidases; D004091:Hydromorphone; D005998:Glycine