为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Memb...为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。展开更多
Objective: To explore the effects of Peiyuan Tongnao(PYTN) Capsule on working memory, the content of glutamic acid, and the expression of NMDA receptor 2 B(NR2 B) in rats with cerebral ischemia. Materials and Methods:...Objective: To explore the effects of Peiyuan Tongnao(PYTN) Capsule on working memory, the content of glutamic acid, and the expression of NMDA receptor 2 B(NR2 B) in rats with cerebral ischemia. Materials and Methods: 52 Sprague-Dawley rats were randomly divided into sham group, model group, nimodipine group, and PYTN group. The bilateral common carotid artery occlusion(BCAO) was performed to establish rat model with cerebral ischemia in the model, nimodipine, and PYTN groups. Gastric lavage with some drug based on body weight conversion was performed daily for 4 weeks in the nimodipine and PYTN groups. The working memory of the rats was tested by Morris water maze. The expression of Nissl body in hippocampus tissue was observed by Nissl staining. The determination of Glu content in hippocampus was detected by high-performance liquid chromatography. The expression level of NR2 B in hippocampus area was determined using Western blot. Results: Morris water maze test on working memory escape latency. In the model group, day 1 versus day 4, there was a statistical difference(P < 0.05). In the nimodipine group, day 1 vs. day 4 displayed a statistical difference(P < 0.05).In the PYTN group, day 1 versus day 3 and day 1 versus day 4 were in significant differences(P < 0.05). The Glu content in hippocampus of the sham group was significantly different from that of model group(P < 0.05). The Glu content in the PYTN group was significantly different from that of the model group(P < 0.05). With regard to the expression of NMDA 2 B in hippocampus between the sham group and the model, nimodipine, and PYTN groups, all were displayed statistical significance(P < 0.01). As the same, the expression of NMDA2 B in the model group was significant from that of the nimodipine group(P < 0.05) and PYTN group(P < 0.01). Conclusion: PYTN capsule was beneficial for improving working memory and protect neural cells in rats of cerebral ischemia, which may be associated with upregulation of the expression of Glu and NMDAR2 B in hippocampus.展开更多
Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in op...Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in opiate addiction is still unclear. Glu R2-3Y,an interfering peptide, prevents the endocytosis of AMPARs containing the Glu R2 subunit. In this study, we explored the effect of intravenous injection of Glu R2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference(m CPP) in rats. We found that infusion of Glu R2-3Y(1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of m CPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of m CPP. Injection of Glu R2-3Y(1.5 nmol/g) after m CPP extinction blocked the morphine-induced reinstatement of m CPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.展开更多
文摘为探究脯氨酸(Proline,Pro)、谷氨酸(Glutamic Acid,Glu)二肽与鲜味受体分子相互作用,该研究合成了12个Pro、Glu二肽,以感官评价为基础,利用同源建模、分子对接技术研究Pro、Glu二肽与味觉受体第一家族亚型1(Taste Receptor Type 1 Member 1,T1R1)、味觉受体第一家族亚型3(Taste Receptor Type 1 Member 3,T1R3)和钙敏感受体(Calcium Sensitive Receptor,CaSR)的构效关系。结果表明:除脯氨酸-丝氨酸(Proline-serine,Pro-Ser)、缬氨酸-脯氨酸(Valine-proline,Val-Pro)和亮氨酸-谷氨酸(Leucine-glutamic Acid,Leu-Glu)不呈鲜,其余二肽的呈鲜阈值均低于谷氨酸钠阈值(0.3 mg/mL),其中γ-谷氨酸-蛋氨酸(γ-Glutamic Acid-methionine,γ-Glu-Met)和甘氨酸-谷氨酸(Glycine-glutamic Acid,Gly-Glu)的呈鲜阈值最低,为0.07 mg/mL。二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277,T1R1是Glu二肽呈鲜的重要受体;与T1R3的关键结合位点为Glu45、Ser147、Val277和His278,Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点;与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275,Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合,呈味较强的二肽在对接时多嵌于受体结合口袋深处;呈味较弱的二肽有的位于结合口袋较浅的位置,有的其疏水区或亲水区暴露于受体表面。该研究有助于阐明鲜味肽与鲜味受体相互作用机制,为深入研究鲜味肽呈鲜机理奠定基础。
文摘Objective: To explore the effects of Peiyuan Tongnao(PYTN) Capsule on working memory, the content of glutamic acid, and the expression of NMDA receptor 2 B(NR2 B) in rats with cerebral ischemia. Materials and Methods: 52 Sprague-Dawley rats were randomly divided into sham group, model group, nimodipine group, and PYTN group. The bilateral common carotid artery occlusion(BCAO) was performed to establish rat model with cerebral ischemia in the model, nimodipine, and PYTN groups. Gastric lavage with some drug based on body weight conversion was performed daily for 4 weeks in the nimodipine and PYTN groups. The working memory of the rats was tested by Morris water maze. The expression of Nissl body in hippocampus tissue was observed by Nissl staining. The determination of Glu content in hippocampus was detected by high-performance liquid chromatography. The expression level of NR2 B in hippocampus area was determined using Western blot. Results: Morris water maze test on working memory escape latency. In the model group, day 1 versus day 4, there was a statistical difference(P < 0.05). In the nimodipine group, day 1 vs. day 4 displayed a statistical difference(P < 0.05).In the PYTN group, day 1 versus day 3 and day 1 versus day 4 were in significant differences(P < 0.05). The Glu content in hippocampus of the sham group was significantly different from that of model group(P < 0.05). The Glu content in the PYTN group was significantly different from that of the model group(P < 0.05). With regard to the expression of NMDA 2 B in hippocampus between the sham group and the model, nimodipine, and PYTN groups, all were displayed statistical significance(P < 0.01). As the same, the expression of NMDA2 B in the model group was significant from that of the nimodipine group(P < 0.05) and PYTN group(P < 0.01). Conclusion: PYTN capsule was beneficial for improving working memory and protect neural cells in rats of cerebral ischemia, which may be associated with upregulation of the expression of Glu and NMDAR2 B in hippocampus.
基金supported by grants from the National Natural Science Foundation of China(81171043,31400880)the Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Sciences,China(KLMH2014ZG02)
文摘Accumulating evidence indicates that a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors(AMPARs) are involved in the relapse to abused drugs.However, the role of AMPARs containing the Glu R2 subunit in opiate addiction is still unclear. Glu R2-3Y,an interfering peptide, prevents the endocytosis of AMPARs containing the Glu R2 subunit. In this study, we explored the effect of intravenous injection of Glu R2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference(m CPP) in rats. We found that infusion of Glu R2-3Y(1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of m CPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of m CPP. Injection of Glu R2-3Y(1.5 nmol/g) after m CPP extinction blocked the morphine-induced reinstatement of m CPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.