Pranzatelli M R, Dailey A, Markush S
Neurology Department, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
J Recept Res. 1988;8(5):667-81. doi: 10.3109/10799898809049018.
Thyrotropin releasing hormone (TRH) and serotonin (5-HT) are co-transmitters in spinal and medullary neurons. To study the functional significance of this relationship and the regulation of TRH receptors, we chronically administered TRH and analogs MK-771 and CG-3509 to rats at a dose which evoked behavioral abnormalities. TRH reduced specific binding at spinal (24%) and hypothalamic (31%) TRH receptors and decreased TRH stimulated motor behaviors, such as rearing and cage crossing (locomotion). 5-HT1 and 5-HT2 receptors were unaffected except for an 11% increase in specific binding at spinal 5-HT1 sites. 5-HT and NE concentrations measured by HPLC were not altered in brainstem or hippocampus. In contrast, spinal TRH receptor specific binding increased 11% in rats treated intracisternally with 5,7-dihydroxytryptamine, but the effect was not significant. In competition studies in vitro, MK-771, TRH, and CG-3509 had no activity at 5-HT2 receptors in neocortex, brainstem, or spinal cord, and little activity at 5-HT1 sites (IC 50s greater than 100 uM). A mixed competitive and non-competitive binding profile at 5-HT1 sites resulted in the presence of 100 uM TRH. Conversely, 5-HT agonists had minimal effect at TRH receptors in spinal cord. These data suggest reciprocal or independent regulation of 5-HT1 and TRH receptors in co-transmitter and non-cotransmitter regions, respectively, in response to chronic TRH administration.
促甲状腺激素释放激素（TRH）和5-羟色胺（5-HT）是脊髓和延髓神经元中的共同递质。为了研究这种关系的功能意义以及TRH受体的调节，我们以能诱发行为异常的剂量长期给大鼠施用TRH及其类似物MK-771和CG-3509。TRH降低了脊髓（24%）和下丘脑（31%）TRH受体的特异性结合，并减少了TRH刺激的运动行为，如竖毛和穿越笼子（运动）。5-HT1和5-HT2受体未受影响，只是脊髓5-HT1位点的特异性结合增加了11%。通过高效液相色谱法测定的脑干或海马中的5-HT和去甲肾上腺素浓度未改变。相比之下，经脑池内注射5,7-二羟色胺处理的大鼠脊髓TRH受体特异性结合增加了11%，但效果不显著。在体外竞争研究中，MK-771、TRH和CG-3509在新皮质、脑干或脊髓的5-HT2受体上无活性，在5-HT1位点的活性也很小（半数抑制浓度大于100μM）。在5-HT1位点存在100μM TRH时呈现混合竞争和非竞争结合模式。相反，5-HT激动剂对脊髓中的TRH受体影响极小。这些数据表明，在共同递质和非共同递质区域，分别对长期施用TRH做出反应时，5-HT1和TRH受体存在相互或独立的调节。
