精氨酸加压素对大鼠视前区GABA_A受体亚单位磷酸化的影响

目的:研究精氨酸加压素(AVP)对大鼠视前区γ-氨基丁酸(GABA)A型受体(GABA_A受体)亚单位(α、β和γ2)表达和磷酸化的影响。方法:实验分为对照组、AVP组、V1a受体抑制剂+AVP组和V1a受体抑制剂组(均n=10);腹腔注射AVP或V1a受体抑制剂0.5 h后,采用RT-qPCR和Western blot法检测视前区GABA_A受体亚单位(α、β和γ2)表达及磷酸化的变化。结果:与对照组相比,AVP或V1a受体抑制剂组大鼠视前区GABA_A受体亚单位表达均无显著变化;AVP能显著上调视前区GABA_A受体γ2亚单位的磷酸化水平(P0.05);AVP显著增加蛋白激酶C(PKC)和钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)表达和磷酸化(P0.01)。结论:外源性AVP不影响GABA_A受体亚单位(α、β和γ2)表达,但主要通过V1a受体激活PKC和CaMKⅡ,影响γ2亚单位磷酸化水平,从而调制视前区GABA_A受体介导的抑制性突触传递。

Effects of arginine vasopressin on subunit phosphorylation of GABAA receptors in rat preoptic area

AIM: To investigate the effects of arginine vasopressin (AVP) on the expression and phosphorylation of γ-aminobutyric acid (GABA) subtype A receptor (GABA_A receptor) subunits in the preoptic area (POA) of rats. METHODS: The rats were divided into AVP group (n=10), AVP+V1a receptor blocker group (n=10), V1a receptor blocker group (n=10) and control group (n=10). After intraperitoneal injection of AVP or V1a receptor antagonist for 0.5 h, the changes of the expression and phosphorylation of POA GABA_A receptor subunits (α, β and γ2) were analyzed by RT-qPCR and Western blot. RESULTS: Compared with control group, no significant change of GABA_A receptor subunit expression in the rats injected with AVP or V1a receptor antagonist was observed. AVP up-regulated the phosphorylation level of POA GABA_A receptor γ2 subunit (P<0.05), and significantly increased the expression and phosphorylation of protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ). CONCLUSION: Exogenous AVP has no effect on expression of POA GABA_A receptor subunits (α, β and γ2) and is involved in modulation of GABAergic synaptic transmission in the POA by activation of PKC and CaMKⅡ and phosphorylation of γ2 subunit via V1a receptor.