LEAD INHIBITS CA2+-STIMULATED NITRIC-OXIDE SYNTHASE ACTIVITY FROM RAT CEREBELLUM

被引:34
作者
QUINN, MR
HARRIS, CL
机构
[1] Laboratory of Neurotransmitter Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314
关键词
LEAD; NITRIC OXIDE SYNTHASE; NITRIC OXIDE; CA2+-CALMODULIN; BRAIN NOS; NOS INHIBITOR; HEAVY METAL TOXICANT;
D O I
10.1016/0304-3940(95)11845-N
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Pb2+ is reported to cause cognitive dysfunctions in children and to inhibit long-term potentiation (LTP), a model form of synaptic plasticity that involves nitric oxide (NO). Since Pb2+ interacts with Ca2+-calmodulin, and brain nitric oxide synthase (NOS) is Ca2+-calmodulin regulated, we examined the effects of Pb2+ on NOS activity prepared from rat cerebellum. NOS required NADPH and was inhibited by monomethylarginine. Full NOS activity required 0.6 mu M free Ca2+ and was inhibited 50% by 17 nM and 100% by 80 nM free Pb2+. NOS inhibition by Pb2+ was reversible by increasing free Ca2+ concentrations. Evaluation of other divalent cations resulted in the following ranked order of potencies: CU2+ > Pb2+ >> Zn2+; Fe2+, Ba2+, Mg2+, Mn2+, and Sr2+ were ineffective. These results suggest that Pb2+ inhibition of brain NOS activity may account for some of the effects of Pb2+ on the CNS.
引用
收藏
页码:65 / 68
页数:4
相关论文
共 28 条