Receptor mechanisms mediating cyanide generation in PC 12 cells and rat brain

被引:19
作者
Gunasekar, PG [1 ]
Prabhakaran, K [1 ]
Li, L [1 ]
Zhang, L [1 ]
Isom, GE [1 ]
Borowitz, JL [1 ]
机构
[1] Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, Neurotoxicol Lab, W Lafayette, IN 47907 USA
关键词
protein kinase C; atropine; naloxone; hydromorphone; carbachol; chelerythrine; opiate receptors; muscarinic receptors;
D O I
10.1016/j.neures.2004.01.006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 PC 12 cells. Cyanide generation by a muscarinic agonist in PC 12 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. (C) 2004 Elsevier Ireland Ltd and The Japan NeUroscience Society. All rights reserved.
引用
收藏
页码:13 / 18
页数:6
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