Wang Yu-Feng, Hatton Glenn I
Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA.
J Neurophysiol. 2006 Jun;95(6):3933-47. doi: 10.1152/jn.01267.2005. Epub 2006 Mar 22.
In nonneuronal tissues, activation of oxytocin receptors (OTRs), like other Galpha(q/11) type G-protein-coupled receptors (Galpha(q/11)/GPCRs), increase prostaglandin (PG) expression. This is not known for the OTRs expressed by central OT neurons. We examined mechanisms underlying OT's effects on supraoptic nucleus (SON) OT and vasopressin (VP) neurons in hypothalamic slices from lactating rats. OT application (10 pM, 10 min) significantly increased firing rates of OT and VP neurons, both of which expressed OTRs. Indomethacin, an inhibitor of PG synthetases, blocked these increases. OTR (but not a V1 receptor) antagonist blocked OT effects without blocking the excitatory effect of PGE2. Tetanus toxin blocked OT effects on fast synaptic inputs and firing activity of SON neurons but not OT-evoked depolarization, suggesting involvement of both pre- and postsynaptic neurons. Indomethacin also blocked the excitatory effects of phenylephrine, another Galpha(q/11)/GPCR activating agent but not those of PGE2, a non-Galpha(q/11)/GPCR activating agent in the SON. OT or phenylephrine, but not glutamate or KCl, enhanced cyclooxygenase 2 expression at cytosolic loci in SON neurons and nearby astrocytes, as revealed by immunocytochemistry. This OT effect was not blocked by TTX. Western blot analyses showed that OT significantly increased cyclooxygenase 2 but not actin expression. OT promoted the formation of filamentous actin (F-actin) networks at membrane subcortical areas of both OT and VP neurons. Indomethacin blocked enhancement of F-actin networks by OT but not by PGE2. These results indicate that PGs serve as a common mediator of Galpha(q/11)/GPCR-activating agents in neuronal function.
在非神经组织中，与其他Gα(q/11)型G蛋白偶联受体（Gα(q/11)/GPCRs）一样，催产素受体（OTRs）的激活会增加前列腺素（PG）的表达。中枢OT神经元表达的OTRs是否如此尚不清楚。我们研究了催产素（OT）对哺乳期大鼠下丘脑切片视上核（SON）中OT和血管加压素（VP）神经元作用的潜在机制。施加OT（10 pM，10分钟）显著增加了OT和VP神经元的放电频率，这两种神经元均表达OTRs。PG合成酶抑制剂吲哚美辛可阻断这些增加。OTR拮抗剂（而非V1受体拮抗剂）可阻断OT的作用，但不阻断PGE2的兴奋作用。破伤风毒素可阻断OT对SON神经元快速突触输入和放电活动的影响，但不阻断OT诱发的去极化，提示突触前和突触后神经元均参与其中。吲哚美辛也可阻断去氧肾上腺素（另一种Gα(q/11)/GPCR激活剂）的兴奋作用，但不阻断SON中PGE2（一种非Gα(q/11)/GPCR激活剂）的兴奋作用。免疫细胞化学显示，OT或去氧肾上腺素可增强SON神经元和附近星形胶质细胞胞质位点的环氧化酶2表达，但谷氨酸或氯化钾则无此作用。这种OT效应不受TTX阻断。蛋白质印迹分析表明，OT显著增加环氧化酶2的表达，但不增加肌动蛋白的表达。OT促进了OT和VP神经元膜下皮质区域丝状肌动蛋白（F-肌动蛋白）网络的形成。吲哚美辛可阻断OT对F-肌动蛋白网络的增强作用，但不阻断PGE2的作用。这些结果表明，PGs在神经元功能中作为Gα(q/11)/GPCR激活剂的共同介质发挥作用。
