嘌呤P_2受体激动剂ATP对血管张力的调节作用

目的：研究嘌呤Ｐ２受体激动剂ＡＴＰ对血管张力的影响及其药理学特征。方法：大鼠离体主动脉环实验。结果与结论：大鼠主动脉的内皮细胞和平滑肌细胞分别存在Ｐ２ｘ和Ｐ２ｙ受体，ＡＴＰ对血管张力产生的影响取决于血管所处的张力状态：内皮细胞完整的大鼠离体主动脉标本处于收缩状态时，ＡＴＰ通过激活内皮细胞的Ｐ２ｙ受体，诱发内皮依赖性舒血管反应；去除内皮细胞的大鼠离体主动脉标本处于静息状态时，ＡＴＰ作用于血管平滑肌细胞的Ｐ２ｘ受体，诱发非内皮依赖性血管收缩反应。

ROLE OF BIVALENT CATIONS AND CHOLINE IN ATP-INDUCED APOPTOSIS OF HUMAN LYMPHOCYTES WITH P2Z RECEPTORS

The role of bivalent cations and choline in ATP induced apoptosis via P2Z purinoceptor was investigated in human leukemic lymphocytes. In vitro exposure of leukemic lymphocytes with P2Z receptors to 1 mmol/L ATP or 0 1 mmol/L benzoylbenzoic ATP(BzATP) for 8 h in the presence of choline, 1 mmol/L Mg 2+ or other bivalent cations, and ATP induced DNA breaks, associated with apoptosis were quantified by TdT assay. We observed that (1) Extracellular Mg 2+ or Ca 2+ stimulated ATP induced DNA fragmentation in a dose dependent manner, and the compatible evidence was provided by the inhibition of ATP induced DNA fragmentation in the present of EGTA or EDTA; (2) ATP induced DNA fragmentation was completely inhibited by 1 mmol/L Zn 2+ ;(3)ATP induced DNA breaks were not affected by Ba 2+ , Sr 2+ , Co 2+ when they were substituted for extracellular Mg 2+ or Ca 2+ ;(4)Choline, an inhibitor of phospholipase D(PLD) stimulated by ATP through P2Z receptor in human lymphocytes, was also a partial inhibitor of ATP induced DNA fragmentation, and the results were confirmed by flow cytometric analysis (FCA); (5)ATP induced DNA fragmentation was completely obliterated when the temperature was lower than 10℃. These results suggest that the endonuclease and PLD may be involved in ATP induced apoptosis in human lymphocytes via P2Z receptor.

Nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function

In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

P2Y6 receptor and immunoinflammation

The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin （IL）-8 from monocytes and macrocytes. So there raises a question： whether purinoceptor P2Y6 also takes part in neuroinflammation？ Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including （1） structure of purinoceptor P2Y6; （2） distribution and properties of purinoceptor P2Y6; （3） relationships between purinoceptor P2Y6 and microglia; （4） relationships between purinoceptor P2Y6 and immunoinflammation. It＇s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.

Inhibition of P2X_7 Receptor by Extracts of Chinese Medicine

Objective： To investigate the influence of Acorus gramineus （Soland）, a crude extract, SCP01, and a purified component, SCP02, and of Rosmarinus officinalis L., X0728 on human mast cells （HMC-1 Cell Line）. Methods： Current-voltage of P2X7 receptors on human mast cell membrane activated by ATP was recorded by the whole-cell patch clamp technique. Results： The current at -100 mV mediated by P2X7 was inhibited by （27.6 ± 2.0） % in the presence of 40 μg/mL SCP01 and by （29.5 ± 2.2） % in the presence of 40 μg/mL SCP02, which was identified as α-asarone. 42 μg/mL of the commercially available α-asarone inhibited the P2X7-mediated current by （52.2 ± 2.0） %. In contrast to SCP01 and SCP02, 40 μg/mL X0728 provoked stimulation of the current by （28.6 ± 2.8） %. All effects were voltage- independent. Conclusion： The inhibition of P2X7 by α-asarone will inhibit intracellular calcium increase and this may account for the inhibition of reported excitotoxic cell death. The pharmacological function of P2X7 stimulation by X0728 needs further investigation.