Kline David D, Takacs Kristin N, Ficker Eckhard, Kunze Diana L
Rammelkamp Center for Education and Research, MetroHealth Medical System, Cleveland, Ohio 44109-1998, USA.
J Neurophysiol. 2002 Nov;88(5):2736-44. doi: 10.1152/jn.00224.2002.
10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 +/- 5% of control by DA (100 microM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 microM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 microM), depressed EPSCs to 73 +/- 4% of control. The D2-like receptor antagonist, sulpiride (20 microM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 +/- 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 +/- 2.2 to 6.2 +/- 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.
10.1152/jn.00224.2002。多巴胺（DA）通过外周和中枢机制调节心肺反射。本研究的目的是探讨DA在孤束核（NTS）突触传递中的作用，NTS是心肺反射的主要整合部位。为了研究DA的作用，我们在大鼠水平脑干切片中采用全细胞电压钳记录。孤束刺激诱发的兴奋性突触后电流（EPSCs）在DA（100微摩尔）作用下降低至对照的70±5%。DA使EPSCs降低的同时，配对脉冲抑制率降低，而输入电阻或EPSC衰减几乎没有变化，提示为突触前机制。D1样激动剂SKF 38393 Br（30微摩尔）未改变EPSC幅度，而D2样激动剂盐酸喹吡罗（30微摩尔）使EPSCs降低至对照的73±4%。D2样受体拮抗剂舒必利（20微摩尔）消除了DA对EPSCs的调节作用。最重要的是，单独使用舒必利可使EPSCs增加至对照的131±10%，提示NTS中存在对突触传递的紧张性D2样调节。对自发性EPSCs的检测显示，DA使事件频率从9.4±2.2赫兹可逆性降低至6.2±1.4赫兹。然而，舒必利并未改变自发性事件。NTS切片的免疫组织化学显示，D2受体与突触素和P物质共定位，证实了突触前分布。D2受体也定位于培养的岩神经节神经元，即突触前传入纤维的胞体。在岩神经节神经元中，D2存在于酪氨酸羟化酶免疫阳性的细胞中，提示它们是化学感受性传入纤维。这些结果表明，DA通过突触前D2样机制对NTS中传入感觉纤维与二级中继神经元之间的突触活动进行紧张性调节。
