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1.
Treatment of frog neuromuscular preparations with chlorpromazine (5 mumol/l) resulted in a marked rise in miniature endplate potential (MEPP) frequency of greater than 100% within 30 min, and an increase in evoked transmitter release (quantal content 5-15) of about 35%. Treatment with chlorpromazine sulphoxide (5 microM), a derivative of chlorpromazine with a much lower affinity for calmodulin, had very little effect on either form of transmitter release. It is concluded that stimulatory effects of calmodulin-binding drugs at the nerve terminal may well be exerted through calmodulin inhibition. The stimulatory effect of chlorpromazine on MEPP frequency was markedly reduced in preparations bathed in EGTA-containing Ca2+-free saline, but the response was largely restored by raising the temperature by 3-4 degrees C. It is argued that despite this partial dependence on [Ca2+]o, stimulation of transmitter secretion by chlorpromazine is likely to be mediated by inhibition of calmodulin-activated Ca2+-ATPases, and consequent elevation of [Ca2+]i. 相似文献
2.
目的 探讨钙调素拮抗剂E6的抗脑缺血作用机制。方法 用[3H]-L-Glu(glutamic acid,Glu)标记大鼠脑突触体,测定突触体的Gln释放量和用一氧化氮合酶(nitric oxide synthase,NOS)试剂盒测定成年大鼠脑匀浆上清中NOS活性。结果 E6促进Glu释放(与对照组比,10-5mol·L-1组增加81.0%),但对KCl(50 mmol·L-1)引起的Glu释放有抑制作用,10-5mol·L-1E6的抑制率为23.2%。E6浓度依赖性地抑制NOS活性。钙调素(calmodulin,CaM)(30μg·ml-1)可逆转E6的抑制作用(10-6mol·L-1E6的抑制率为13.7%),N-硝基-精氨酸((N-nitro-arginine,L-NNA)(10μmol·L-1)可加强E6的抑命作用(10-6mol·L-1的抑制率为76.5%)。结论 E6是与CaM结合后发挥抑制 NOS活性效应的,E6对Glu 释放的影响可能与其对NOS活性及其对神经细胞内Ca2+影响有关。 相似文献
3.
目的:研究钙调素拮抗剂亲脂区与亲水区之间连接链最佳的距离。方法:采用Fibonacci寻找法设计并合成了不同长度侧链的1,2-二苯乙烯类钙调素拮抗剂。结果:它们的拮抗活性表明,随着连接亲水部分氨基与亲脂苦环部分的碳链的增长,其活性增强。分子图形学研究显示,随着碳链的增长,氨基与钙调素Glu84,87的羧基的距离缩短,静电相互作用增强,拮抗剂与钙调素的结合能增加,并在碳链个数7左右达到一个极值。结论:在1,2-二苯乙烯类钙调素拮抗剂中,连接亲脂区与亲水区的脂肪链的碳原子的最佳个数在7左右。 相似文献
4.
郭西文 《菏泽医学专科学校学报》2003,15(1):1-3
目的 为观察利多卡因对重型颅脑损伤患血浆降钙素基因相关肽、钙调素水平及其预后的影响。方法 将64例重型颅脑损伤患按随机原则分成利多卡因治疗组和常规治疗组,分别测定治疗前及治疗开始后第2、4、7天血浆CGRP、CaM含量,伤后6个月进行预后判断并进行比较分析。结果 重型颅脑损伤后患血浆CGRP水平下降而CaM水平升高,利多卡因治疗后可使上述改变显减轻并显改善患预后(P<0.05)。结论 重型颅脑损伤后血浆CGRP水平下降而CaM水平升高,参与了继发性脑损伤的病理生理过程,早期应用利多可因治疗可通过对CGRP和CaM水平的影响,减轻继发性脑损伤,发挥脑保护作用。 相似文献
5.
Despite the wide clinical use of lithium in the treatment of manic depressive illness there is no adequate explanation for its mechanism of action. In the light of lithium's suggestive effects on the second messenger system in the brain, we studied the effects of chronic dietary lithium treatment (achieving blood levels in the therapeutic range) on protein phosphorylation in different areas of rat brain. An increase in the phosphorylation of a 64-kDa membrane-associated protein was evident in the lithium-treated rats compared to controls. This increase was observed only under basal phosphorylating conditions and was abolished when the phosphorylation was performed in the presence of Ca2+ or Ca2+ and calmodulin. The possibility that this 64-kDa protein affected by lithium is the beta-subunit of the calmodulin-dependent protein kinase or a different protein which co-migrates with it is discussed. 相似文献
6.
Kinoshita-Kawada M Tang J Xiao R Kaneko S Foskett JK Zhu MX 《Pflügers Archiv : European journal of physiology》2005,450(5):345-354
The transient receptor potential canonical type 5 (TRPC5) channel is a member of the channels that has been implicated in neurite extension and growth cone morphology of hippocampal neurons. Although homomeric TRPC5 channels are activated following stimulation of Gq/11-coupled receptors, the exact mechanism for this activation remains unresolved. Using two-electrode voltage clamp recordings, we show that the activity of TRPC5 channels expressed in Xenopus oocytes is dependent on the presence of Ca2+ at the extracellular as well as the cytoplasmic side of the plasma membrane. TRPC5 was activated by the stimulation of coexpressed M5 muscarinic receptors or by ionomycin. The TRPC5 activity was detectable with the presence of submillimolar levels of extracellular Ca2+, but it was eliminated by the injection of 5 mM 1,2-bis(o-aminophenoxy)ethane-N,N,N,N-tetraacetic acid into the oocytes. Lanthanum could substitute for extracellular Ca2+ to support TRPC5 activity. Coexpression of Ca2+-binding protein 1 (CaBP1), but not calmodulin (CaM), inhibited the TRPC5 activity, without affecting the cell surface expression of TRPC5 proteins. Using in vitro binding assays, we demonstrated direction interactions between CaBP1 and TRPC5. The CaBP1-binding sites at the C terminus of TRPC5 are closely localized, but not identical, to CaM-binding sites. We conclude that TRPC5 is a Ca2+-regulated channel, and its activity is negatively controlled by CaBP1. 相似文献
7.
目的探讨巨细胞病毒感染致中枢神经系统功能紊乱的神经生物学机制.方法将BALB/C乳鼠同母鼠随机分为实验对照组(18只)和接种病毒组(35只),感染方法为颅内注射,3个月后检测两组鼠的行为学变化及脑皮质CaMmRNA表达的改变.结果接种病毒组小鼠学习记忆能力下降,皮质CaMmRNA表达增加(1.0493±0.32,P<0.01).结论巨细胞病毒感染所引起的脑皮质CaMmRNA表达增高可能是其神经系统发育异常的神经生物学机制之一. 相似文献
8.
Sylviane Tardivel Lea Razanamaniraka Tilman Drüeke Bernard Lacour 《Pflügers Archiv : European journal of physiology》1995,429(4):470-476
The effect of sorbitol on Ca uptake by isolated ileal epithelial cells was investigated. Intestinal cells were isolated from rat ileum by mechanical vibration.45Ca uptake was approximately 2 times higher in cells exposed to 200 mM sorbitol ofd-alanine than in control cells. This enhancing effect of sorbitol on percentage Ca uptake decreased with increasing Ca concentrations in the incubation medium suggesting an effect on Ca entry velocity. The addition of 10 M nifedipine or 200 M verapamil to the incubation medium was devoid of any effect on Ca uptake in ileal cells, whereas 100 M trifluoperazine or chlorpromazine abolished the stimulatory effect of sorbitol. Finally, the effect of sorbitol on isolated cells was independent of a measurable change of cellular ATP content. In conclusion, the stimulatory effect of sorbitol on ileal Ca uptake is probably exerted through mechanisms other than an increase in intracellular ATP concentration. Sorbitol may enhance enterocyte Ca transport via a direct interaction with calmodulin and/or the Ca pump. It may also exert its effect through an inhibition of the basolateral Na Ca exchanger. 相似文献
9.
In chemically skinned chicken gizzard smooth muscle fibers investigated shortly after preparation, a contraction may be induced by calcium and calmodulin which is independent of myosin phosphorylation at intermediate Ca2+-concentrations. However, fibers stored for a prolonged period also contract in the absence of exogenous calmodulin and exhibit a close relationship between force development and myosin phosphorylation. 相似文献
10.
钙调素对微管组装的调节作用 总被引:1,自引:1,他引:1
利用我们建成的钙调素表达可调细胞模型-RC3细胞,对CaM高表达时微管组装行为进行了研究,当用生理剂量的地塞米松处理RC3细胞,细胞内CaM水平提高,而管蛋白浓度没有变化,造成钙调素/管蛋白比值上升,MT解聚,但同时加入CaM拮抗剂三氟拉嗪处理时,则可抑制MT的解聚,C3H10T1/2转化细胞CaM含量的增加是引起MT解聚的主要因素,TFP处理可恢复MT组装。RC3细胞CaM高表达导致MT解聚的实 相似文献