Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
AIM： To quantify changes in urinary excretion of aquaporin2 water channels （u-AQP2）, the sodium-potassium-chloride co-transporter （u-NKCC2） and the epithelial sodium channels （u-ENaC） during treatment with bend...AIM： To quantify changes in urinary excretion of aquaporin2 water channels （u-AQP2）, the sodium-potassium-chloride co-transporter （u-NKCC2） and the epithelial sodium channels （u-ENaC） during treatment with bendrofumethiazide （BFTZ）, amiloride and placebo.METHODS： In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fuid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC （u-ENaCγ）, and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin （p-AVP）, renin （PRC）, angiotensin Ⅱ （p-ANG Ⅱ） and aldosterone （p-Aldo） were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fuid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.RESULTS： At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang Ⅱ and p-Aldo were increased during active treatments （P 〈 0.001）. After hypertonic saline, u-NKCC2 increased during amiloride （6% ± 34%; P = 0.081） and increased significantly during placebo （17% ± 24%; P = 0.010）. U-AQP2 increased signifcantly during amiloride （31% ± 22%; P 〈 0.001） and placebo （34% ± 27%; P 〈 0.001）, while u-NKCC2 and u-AQP2 did not change signifcantly during BFTZ （-7% ± 28%; P = 0.257 展开更多
The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophys...The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.展开更多
Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cot...Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cotransporter （ NCC）, and the Cl^- channel （ CLC ）-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2.Methods Sprague Dawleys rats were treated subcutaneously with either Ang Ⅱ （100 ng·kg^-1·min^-1） or vehicle for 14 days. Expression of NKCC2, NCC and CLC-K2 mRNA in kidneys was determined by real time polymerase chain reaction （PCR）. Western blotting analysis was used to measure NKCC2 and NCC protein expression.Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold （P 〈 0.05 ） . There were no changes in NCC mRNA or protein expression in AngⅡ-treated rats versus control.Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na^＋ and Cl^- reabsorption in response to Ang Ⅱ.展开更多
目的:考察葡萄糖氯化钠钾注射液(GNK)与7种儿童常用药物配伍的稳定性。方法:将 GNK 与7种药物模拟临床用药浓度分别配伍,采用高效液相色谱法分别洲定0,1,2,4,6,8 h 的药物含量,同时观察其外观变化,并测定 pH 及不溶性微粒数日。结果:GNK...目的:考察葡萄糖氯化钠钾注射液(GNK)与7种儿童常用药物配伍的稳定性。方法:将 GNK 与7种药物模拟临床用药浓度分别配伍,采用高效液相色谱法分别洲定0,1,2,4,6,8 h 的药物含量,同时观察其外观变化,并测定 pH 及不溶性微粒数日。结果:GNK 与7种药物配伍的供试品溶液在8 h 内性状稳定,不溶性微粒数目符合药典规定,pH 和药物含量均无明显变化。结论:GNK 与7种药物配伍的供试品溶液在8 h 内稳定。展开更多
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
基金Supported by Grants from The Lundbeck FoundationAase and Ejnar Danielsens Foundation+1 种基金Helen and Ejnar Bjoernows FoundationRegion Midjutlands Research Fund
文摘AIM： To quantify changes in urinary excretion of aquaporin2 water channels （u-AQP2）, the sodium-potassium-chloride co-transporter （u-NKCC2） and the epithelial sodium channels （u-ENaC） during treatment with bendrofumethiazide （BFTZ）, amiloride and placebo.METHODS： In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fuid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC （u-ENaCγ）, and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin （p-AVP）, renin （PRC）, angiotensin Ⅱ （p-ANG Ⅱ） and aldosterone （p-Aldo） were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fuid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.RESULTS： At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang Ⅱ and p-Aldo were increased during active treatments （P 〈 0.001）. After hypertonic saline, u-NKCC2 increased during amiloride （6% ± 34%; P = 0.081） and increased significantly during placebo （17% ± 24%; P = 0.010）. U-AQP2 increased signifcantly during amiloride （31% ± 22%; P 〈 0.001） and placebo （34% ± 27%; P 〈 0.001）, while u-NKCC2 and u-AQP2 did not change signifcantly during BFTZ （-7% ± 28%; P = 0.257
基金supported by the Science and Technology Foundation of Guangdong Province,No.2008B060600063the National Natural Science Foundation of China,No. 81071050the Natural Science Foundation of Guangdong Province,No. S2011020005483
文摘The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.
文摘Background Little information is available regarding the effect of angiotensin Ⅱ （Ang Ⅱ ） on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter （NKCC2 ）, the thiazide-sensitive sodiumchloride cotransporter （ NCC）, and the Cl^- channel （ CLC ）-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2.Methods Sprague Dawleys rats were treated subcutaneously with either Ang Ⅱ （100 ng·kg^-1·min^-1） or vehicle for 14 days. Expression of NKCC2, NCC and CLC-K2 mRNA in kidneys was determined by real time polymerase chain reaction （PCR）. Western blotting analysis was used to measure NKCC2 and NCC protein expression.Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold （P 〈 0.05 ） . There were no changes in NCC mRNA or protein expression in AngⅡ-treated rats versus control.Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na^＋ and Cl^- reabsorption in response to Ang Ⅱ.
文摘目的:考察葡萄糖氯化钠钾注射液(GNK)与7种儿童常用药物配伍的稳定性。方法:将 GNK 与7种药物模拟临床用药浓度分别配伍,采用高效液相色谱法分别洲定0,1,2,4,6,8 h 的药物含量,同时观察其外观变化,并测定 pH 及不溶性微粒数日。结果:GNK 与7种药物配伍的供试品溶液在8 h 内性状稳定,不溶性微粒数目符合药典规定,pH 和药物含量均无明显变化。结论:GNK 与7种药物配伍的供试品溶液在8 h 内稳定。
