香茶菜甲素酯对依赖钙调素的环核苷酸磷酸二酯酶的抑制作用

香茶菜甲素酯是香茶菜甲素的一种新的衍生物。研究发现该化合物能明显抑制CaM激活的PDE活性,其IC_(50)为75μmol/L。抑制动力学测定表明它以非竞争方式拮抗CaM对PDE的活化。CaM荧光测定显示,香茶菜甲素酯可以降低ca~(2+)诱导的CaM酪氨酸荧光强度,提示它可能通过改变Ca~(2+)—CaM构象而抑制CaM—PDE。     

Calmodulin-dependent adenylate cyclase in rat retina and the response to dopamine

Adenylate cyclase activity from the rat neural retina was highly stimulated with Ca²⁺ and calmodulin. The retinal adenylate cyclase activity was also increased by dopamine, and the activation was not changed with or without Ca²⁺-calmodulin in fractions from the neural retina homogenate after sucrose density gradient centrifugation. The results suggest that the two regulation systems (i.e. dopamine and Ca²⁺-calmodulin) of adenylate cyclase in the rat retina appear to be independent.     

Evidence for a calmodulin inhibitory substance(s) isolated from human meningiomas

Summary Calmodulin (CaM), a calcium-binding protein, is present in human tumor tissues and in meningioma. Following a purification procedure using DEAE-cellulose and the polymeric resin 3520, the CaM content of tumor extracts was assayed using CaM-deficient phosphodiesterase (PDE). In the presence of low amounts of the extracts, a concentration dependent stimulation of PDE was observed. However, further addition of higher concentrations of the extract produced a marked inhibition of the CaM stimulation of PDE in 13 of 15 specimens. A wide range (2.44–51.31 units/1 mg tumor [wet weight]) of inhibitor concentration was noted. However, no detectable inhibitory activity of this magnitude was observed in normal human meningeal extracts. The final extracts showed no calcineurin-phosphatase activity in the presence of Ni⁺⁺, a known activator of this phosphatase. SDS-polyacrylamide gel (10%) electrophoresis of the extracts revealed the typical calmodulin band at 17 kDa plus two additional bands with apparent molecular masses of 21 and 36 kDa respectively. These bands were not seen using normal meningeal extracts.     

Cardiac ischaemic stress: cardiomyocyte Ca²⁺, sex and sex steroids

1. Important sex differences exist in ischaemic heart disease. Oestrogen has been conventionally regarded as providing a cardioprotective benefit and testosterone frequently perceived to exert a deleterious effect. However, there is accumulating evidence that argues against this simple dichotomy, suggesting that the influence of oestrogen and testosterone conferring benefit or detriment may be context specific. 2. Cardiomyocyte calcium (Ca(2+)) loading is recognized to be a major factor in acute ischaemia-reperfusion pathology, promoting cell death, contractile dysfunction and arrhythmogenic activity. Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a mediator of many of the cardiomyocyte Ca(2+)-related pathologies in ischaemia-reperfusion. Cardiomyocyte Ca(2+)-handling processes have been shown to be modulated by the actions of oestrogen and testosterone. A role for these sex steroids in influencing CaMKII activation is argued. 3. Although many experimental studies of oestrogen manipulation can identify a cardioprotective role for this sex steroid, there are also numerous reports that fail to demonstrate sex differences in postischaemic recovery. Experimental studies report that testosterone can be protective in ischaemia-reperfusion in males and females in some settings. 4. Further studies of sex steroid influence in the ischaemic heart will allow the development of therapeutic interventions that are specifically targeted for male and female hearts.     

Neurogranin phosphorylation fine-tunes long-term potentiation

Learning-related potentiation of synaptic strength at Cornu ammonis subfield 1 (CA1) hippocampal excitatory synapses is dependent on neuronal activity and the activation of glutamate receptors. However, molecular mechanisms that regulate and fine-tune the expression of long-term potentiation (LTP) are not well understood. Recently it has been indicated that neurogranin (Ng), a neuron-specific, postsynaptic protein that is phosphorylated by protein kinase C, potentiates synaptic transmission in an LTP-like manner. Here, we report that a Ng mutant that is unable to be phosphorylated cannot potentiate synaptic transmission in rat CA1 hippocampal neurons and results in a submaximal expression of LTP. Our results provide the first evidence that the phosphorylation of Ng can regulate LTP expression.     

腈双吡啉对离体血管舒张的机理

腈双吡啉是从氨利酮与米利酮的合成衍生物中筛选出的强心扩血管药,离体实验表明它能拮抗高K~+、去甲肾上腺素(NE)收缩家兔主动脉环的作用,使NE,CaCl_2的量效曲线右移;在高浓度时降低最大收缩效应。它能增强钙调蛋白拮抗剂拮抗NE引起的家兔主动脉环收缩。结果表明它对NE收缩离体血管的量效曲线不同于选择性阻断α受体的药物妥拉唑啉的作用,也不同于典型的钙拮抗剂维拉帕米的作用,而可能是钙调蛋白的非竞争性拮抗剂。     

Involvement of calmodulin in platelet reaction

Penothiazines, known as selective inhibitors of calmodulin, completely inhibited platelet aggregation and secretion induced by ADP, collagen, epinephrine, thrombin or calcium ionophore. They also completely inhibited aggregation induced by exogenous arachidonate (AA) or a mixture of thromboxane A₂ and prostaglandin endoperoxides (TxA₂/PG G₂,H₂). Also, in the presence of these calmodulin inhibitors, the release of AA from platelet phospholipids (PL) was dosedependently inhibited in stimulated platelets. These observations suggest that in platelet reaction, calmodulin is involved in at least two different steps of the reaction: activation of phospholipases and contraction of platelet actomyosin after the formation of TxA₂.     

Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions.

Calcium stimulates, and zinc inhibits, a wide variety of cell types. In the erythrocyte, we have found calcium and zinc to have antagonist actions in a variety of systems. An important mechanism for calcium effects on cells is activation of calmodulin. Calmodulin is a small ubiquitous protein which, when activated by calcium, has a large array of cellular regulatory functions. We now report that calmodulin function is inhibited by low concentrations of zinc. Zinc inhibition of calmodulin provides a rational molecular mechanism for the diverse cellular inhibitory effects of zinc, as well as for zinc's antagonism of calcium effects.