Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Met...Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Methods The VSMCs derived from aortae of SHR and Wistar Kyoto (WKY) rats were loaded for 48 hours with myo inositol. Inositol phosphate release was initiated by the addition of 10 5 mol/L norepinephrine in intact cells or by guanosine 5' 0 (3 thio tri sphosphate) (GTP gamma S) in permeabilized cells. In the meantime, growth arrested VSMCs were stimulated by 10% calf serum for 0, 30, 45, or 60 min, then gene expressions of Gq alpha subunit (G alph a q) were observed. Results There were no significant differences in inositol 1, 4,5 triphosphate (IP 3) level and expression of G alpha q mRNA between quiescent VSMCs from SHR and that from WKY. When stimulated by norepinephrine, IP 3 production increased transiently with a peak level at 10 s in VSMCs from WKY, and a rapid biphasic IP 3 response, which was significantly higher than that of WKY, in VSMCs from SHR had been observed. G proteins activated by GTP gamma S significantly raised IP 3 production in VSMCs from SHR compared to WKY (SHR vs WKY: 234.8%±29.2% vs 142.4%±12.0% of basal IP 3, P<0.05). In addition, the serum effect showed an significant increase in expression of G alpha q mRNA in VSMCs from SHR. Conclusions The hereditary factors are not the only variable regulating IP 3 metabolism and G alpha q gene expression. Influences of multi environmental factors such as vasoactive compounds, together with genetic predisposition, palys an important role in the highly sensitive response of IP 3 production and G alpha q gene over expression in SHR.展开更多
Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current ...Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental ifndings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.展开更多
文摘Abstract Objecitve To explore whether phosphoinositide specific phospholipase C (PLC) activation via G protein in vascular smooth muscle cells (VSMCs) is altered in spontaneously hypertensive rats (SHR). Methods The VSMCs derived from aortae of SHR and Wistar Kyoto (WKY) rats were loaded for 48 hours with myo inositol. Inositol phosphate release was initiated by the addition of 10 5 mol/L norepinephrine in intact cells or by guanosine 5' 0 (3 thio tri sphosphate) (GTP gamma S) in permeabilized cells. In the meantime, growth arrested VSMCs were stimulated by 10% calf serum for 0, 30, 45, or 60 min, then gene expressions of Gq alpha subunit (G alph a q) were observed. Results There were no significant differences in inositol 1, 4,5 triphosphate (IP 3) level and expression of G alpha q mRNA between quiescent VSMCs from SHR and that from WKY. When stimulated by norepinephrine, IP 3 production increased transiently with a peak level at 10 s in VSMCs from WKY, and a rapid biphasic IP 3 response, which was significantly higher than that of WKY, in VSMCs from SHR had been observed. G proteins activated by GTP gamma S significantly raised IP 3 production in VSMCs from SHR compared to WKY (SHR vs WKY: 234.8%±29.2% vs 142.4%±12.0% of basal IP 3, P<0.05). In addition, the serum effect showed an significant increase in expression of G alpha q mRNA in VSMCs from SHR. Conclusions The hereditary factors are not the only variable regulating IP 3 metabolism and G alpha q gene expression. Influences of multi environmental factors such as vasoactive compounds, together with genetic predisposition, palys an important role in the highly sensitive response of IP 3 production and G alpha q gene over expression in SHR.
基金supported by the National Natural Science Foundation of China,No.31271198 and 81121001grants from the Shanghai Committee of Science and Technology,No.11ZR1415900the State Key Laboratory of Medical Neurobiology,Fudan University,No.10-12
文摘Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental ifndings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.
