目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上...目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上P2X嘌呤受体各亚型的表达。结果SD大鼠膀胱中的ICCs细胞主要集中于黏膜下层、肌束边缘以及肌束间,并相互连接呈网络状分布。在7种P2X嘌呤受体亚型中,ICCs细胞上可检测到P2X2和P2X5两种亚型表达。结论大鼠膀胱ICCs细胞可表达P2X2和P2X5两种嘌呤受体亚型,从功能学上证实嘌呤能信号对ICCs细胞功能有影响。展开更多
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...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.展开更多
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. P...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.展开更多
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). Method...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.展开更多
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 rec...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.展开更多
文摘目的探讨P2X嘌呤受体各亚型在大鼠膀胱ICCs细胞(interstitial cells of Cajal,ICCs)的表达及意义。方法制备SD大鼠膀胱组织铺片及冰冻切片,通过免疫荧光法检测大鼠膀胱组织内ICCs细胞分布情况,并进一步采用免疫荧光双标法检测ICCs细胞上P2X嘌呤受体各亚型的表达。结果SD大鼠膀胱中的ICCs细胞主要集中于黏膜下层、肌束边缘以及肌束间,并相互连接呈网络状分布。在7种P2X嘌呤受体亚型中,ICCs细胞上可检测到P2X2和P2X5两种亚型表达。结论大鼠膀胱ICCs细胞可表达P2X2和P2X5两种嘌呤受体亚型,从功能学上证实嘌呤能信号对ICCs细胞功能有影响。
基金This work was supported by the National Institutes of Health,No.NIH P01 HL134609 and R01 HL141198(to JL).
文摘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.
基金supported by the Key Scientific Research Innovation Program of Shanghai Municipal Education Commission,China (No.082260)
文摘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.
基金the Science Foundation of Shanghai Municipal Commission of Science and Technology(05DZ19745,06DZ19732,064319053,07DZ19722,07DZ19733)the National Basic Research Program of China (973 Program,2005CB523306)Shanghai Leading Academic Discipline Project(B112 and T0302)
文摘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.
文摘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.