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1.
Leptin in the CNS: much more than a satiety signal   总被引:12,自引:0,他引:12  
The discovery of the obese gene product, leptin has generated enormous interest in how the periphery signals the status of nutritional stores to specific hypothalamic nuclei involved in regulating feeding and energy balance. However it is emerging that leptin, in addition to its role as a circulating satiety factor, is a multi-faceted hormone that plays a key role in a variety of CNS functions. In this review, we summarise recent progress in leptin biology, with particular focus on its diversity of actions within the CNS, ranging from satiety signal, to regulator of bone formation and inhibitor of neuronal excitability.  相似文献
2.
1. Growth hormone (GH) secretion from pituitary somatotropes is mainly regulated by two hypothalamic hormones, GH-releasing hormone (GHRH) and somatotrophin releasing inhibitory factor (SRIF). 2. Somatotrophin releasing inhibitory factor inhibits GH secretion via activation of specific membrane receptors, somatostatin receptors (SSTRs) and signalling transduction systems in somatotropes. 3. Five subtypes of SSTRs, namely SSTR1, 2, 3, 4 and 5, have been identified, with the SSTR2 subtype divided into SSTR2A and SSTR2B. All SSTRs are G-protein-coupled receptors. 4. Voltage-gated Ca(2+) and K(+) channels on the somatotrope membrane play an important role in regulating GH secretion and SRIF modifies both channels to reduce intracellular free Ca(2+) concentration and GH secretion. 5. Using specific SSTR subtype-specific agonists, it has been found that reduction in Ca(2+) currents by SRIF is mediated by SSTR2 and an increase in K(+) currents is mediated by both SSTR2 and SSTR4 in rat somatotropes.  相似文献
3.
目的通过比较对不同跨膜离子电流作用的效能、效价,探讨传统中药苦参碱抗心律失常作用弱于西药奎尼丁、维拉帕米的原因,确定苦参碱作用的最佳靶点.方法应用全细胞膜片钳技术记录大鼠单个心室肌细胞动作电位和离子电流.首先应用乌头碱诱发心肌离子电流改变,然后观察苦参碱、奎尼丁和维拉帕米对乌头碱诱发离子电流和动作电位改变的作用.结果乌头碱1μmol·L-1诱发大鼠单个心室肌细胞动作电位和离子电流显著变化.乌头碱延长动作电位时程同时增加钠、L-型钙电流和内向整流钾电流.苦参碱100μol·L-1恢复乌头碱诱发的改变,但作用弱于奎尼丁和维拉帕米.结论应用乌头碱打破了心室肌细胞离子通道的平衡,而应用苦参碱明显抑制乌头碱诱发的改变,但其效能效价低于常用的奎尼丁和维拉帕米.  相似文献
4.
酸敏感离子通道在缺血性脑损伤中的作用   总被引:8,自引:0,他引:8  
袁凤来  陈飞虎 《药学进展》2006,30(8):337-341
综述近年来有关酸敏感离子通道在缺血性脑损伤中的作用研究,论及酸敏感离子通道在脑中的分布和作用、它的激活以及在缺血性脑损伤中的作用机制及与谷氨酸受体的协同作用.酸敏感离子通道是一类由胞外酸化所激活的阳离子通道,而缺血性脑损伤正是由其引起胞内Ca^2+超载所致,因此抑制其激活可以对抗缺血性脑损伤,为神经系统缺血性损伤的保护及药物治疗研究提供了新思路.  相似文献
5.
Drugs targeting mitochondrial functions to control tumor cell growth   总被引:6,自引:0,他引:6  
Mitochondria, the power houses of the cell, are at the cross-road of many cellular pathways. They play a central role in energy metabolism, regulate calcium flux and are implicated in apoptosis. Mitochondrial dysfunctions have been associated with various physiopathological disorders, especially neurodegenerative diseases and cancer. Structurally diverse pharmacological agents have shown direct effects on mitochondria ultra-structures and functions, either at the DNA level or upon targeting proteins located in the inner or outer mitochondrial membranes. The brief review deals with the molecular targets and mechanisms of action of chemically diverse small molecules acting on specific mitochondrial loci, such as the respiratory chain, DNA biogenesis, potassium channels, the Bcl-2 protein and the permeability transition pores (PTP). Drugs, which specifically compromise the structural and functional integrity of mitochondria, may provide novel opportunities to combat cancer cell proliferation, providing that these molecules can be selectively delivered to tumor sites. Different examples reported here show that mitochondrial insult or failure can rapidly lead to inhibition of cell survival and proliferation. Mitochondrial impairment may be a successful anti-cancer strategy.  相似文献
6.
Acid-sensitive ion channels in gastrointestinal function   总被引:6,自引:0,他引:6  
Deviations from the physiological values of extracellular pH are monitored by multiple acid sensors. Acid-sensing ion channels are activated by moderate acidification, whereas transient receptor potential cation channels, notably TRPV1, are gated by severe acidosis. In contrast, ionotropic purinoceptor (P2X) ion channels, particularly P2X(2), and two-pore domain background K(+) channels, such as TASK, do not directly signal acidification but rather modulate cell membrane excitability in response to acidosis. These acid sensors, which are expressed by afferent neurons, are most relevant to the regulation of acid secretion, foregut motility and mucosal protection, as well as to gastrointestinal disturbances associated with inflammation, ischaemia and stasis.  相似文献
7.
About 20-30% of patients with epilepsy continue to have seizures despite carefully monitored treatment with antiepileptic drugs. The mechanisms explaining why some patients' respond and others prove resistant to antiepileptic drugs are poorly understood. It has been proposed that pharmacoresistance is related to reduced sensitivity of sodium channels in hippocampal neurons to antiepileptic drugs such as carbamazepine or phenytoin. In line with this proposal, a reduced effect of carbamazepine on sodium currents in hippocampal CA1 neurons was found in the rat kindling model of temporal lobe epilepsy (TLE), i.e. a form of epilepsy with the poorest prognosis of all epilepsy types in adult patients. To address directly the possibility that neuronal sodium currents in the hippocampus play a crucial role in the pharmacoresistance of TLE, we selected amygdala-kindled rats with respect to their in vivo anticonvulsant response to phenytoin into responders and nonresponders and then compared phenytoin's effect on voltage-activated sodium currents in CA1 neurons. Furthermore, in view of the potential role of calcium current modulation in the anticonvulsant action of phenytoin, the effect of phenytoin on high-voltage-activated calcium currents was studied in CA1 neurons. Electrode-implanted but not kindled rats were used as sham controls for comparison with the kindled rats. In all experiments, the interval between last kindled seizure and ion channel measurements was at least 5 weeks. In kindled rats with in vivo resistance to the anticonvulsant effect of phenytoin (phenytoin nonresponders), in vitro modulation of sodium and calcium currents by phenytoin in hippocampal CA1 neurons did not significantly differ from respective data obtained in phenytoin responders, i.e. phenytoin resistance was not associated with a changed modulation of the sodium or calcium currents by this drug. Compared to sham controls, phenytoin's inhibitory effect on sodium currents was significantly reduced by kindling without difference between the responder and nonresponder subgroups. Further studies in phenytoin-resistant kindled rats may help to elucidate the mechanisms that can explain therapy resistance.  相似文献
8.
Arachidonic acid and ion channels: an update   总被引:4,自引:0,他引:4  
Arachidonic acid (AA), a polyunsaturated fatty acid with four double bonds, has multiple actions on living cells. Many of these effects are mediated by an action of AA or its metabolites on ion channels. During the last 10 years, new types of ion channels, transient receptor potential (TRP) channels, store-operated calcium entry (SOCE) channels and non-SOCE channels have been studied. This review summarizes our current knowledge about the effects of AA on TRP and non-SOCE channels as well as classical ion channels. It aims to distinguish between effects of AA itself and effects of AA metabolites. Lipid mediators are of clinical interest because some of them (for example, leukotrienes) play a role in various diseases, others (such as prostaglandins) are targets for pharmacological therapeutic intervention.  相似文献
9.
心律失常发病机制研究进展   总被引:4,自引:0,他引:4  
心律失常是心血管疾病常见的临床表现形式,尤其是室性心动过速、心室颤动等恶性心律失常,不但加重原有心脏疾病,还可诱发心源性猝死。目前抗心律失常药物的疗效并不十分理想,总有效率只有30%~60%。人们对心律失常作用机制的认识仍有限,因此,揭示心律失常发生的深层机制,寻找新的作用靶点是抗心律失常研究领域的重点、难点。近年人们发现心房特异性钾离子通道电流IKur、IKAch等参与了心房颤动,这使心房颤动治疗的研究向前推进一步。钙渗漏、缝隙连接蛋白及钙通道自身抗体在心律失常发生中发挥重要作用。这些发现为开发更有效的抗心律失常药物提供了理论基础。近年研究发现,一类调控基因的小分子RNA(microRNA,miRNA)在心血管疾病的发生、发展中起重要作用,特别是对心律失常及其引起的猝死起关键作用。miR-1、miR-133、miR-590等对心肌缺血、心肌梗死伴随的心律失常表现出明显调控作用。miRNA的生物学特性是同时对多个靶点具有调控作用,这使其具有成为理想抗心律失常靶点的潜力,为心律失常及猝死的防治带来希望。  相似文献
10.
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