Receptor mechanisms mediating cyanide generation in PC12 cells and rat brain.
Cyanide is generated in neurons and this report examines the two different receptors which mediate cyanide formation in neuronal tissue. An opiate receptor blocked by naloxone increases cyanide production both in rat brain and in rat pheochromocytoma (PC12) cells. A muscarinic receptor in PC12 cells releases cyanide and the effect is blocked by atropine. In rat brain, in vivo, a muscarinic agonist inhibits cyanide generation, possibly by acting on receptor subtypes different from those in PC12 cells. Cyanide generation by a muscarinic agonist in PC12 cells is blocked by pertussis toxin but that caused by an opiate is not. Thus, two different receptors and two different second messenger systems can mediate cyanide generation in PC12 cells. In parallel with the in vivo data, cultured primary rat cortical cells also show decreased cyanide release following muscarinic stimulation. Both blockade of cyanide generation by muscarinic receptor activation and cyanide release by opiate agonists from cortical cells are pertussis toxin insensitive. Similarly, little cyanide generation was seen following cholera toxin treatment. These data indicate that opiate receptors increase and muscarinic receptors decrease cyanide production in rat brain tissue by G-protein independent mechanisms. This work supports the suggestion that the powerful actions of cyanide may be important for neuromodulation in the CNS.
Gunasekar
P G
PG
Neurotoxicology Laboratory, Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907-1333, USA.
Prabhakaran
K
K
Li
L
L
Zhang
L
L
Isom
G E
GE
Borowitz
J L
JL
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism*; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004091:Hydromorphone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D018679:Cholinergic Agonists; D003486:Cyanides; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D011956:Receptors, Cell Surface; C049425:oxotremorine sesquifumarate; D009270:Naloxone; D010095:Oxotremorine; D009020:Morphine; D001285:Atropine; D002217:Carbachol; D037342:Pertussis Toxin; D004091:Hydromorphone