Hedner J, Hedner T, Wessberg P, Lundberg D, Jonason J
Acta Physiol Scand. 1983 Mar;117(3):427-37. doi: 10.1111/j.1748-1716.1983.tb00017.x.
Respiratory activity was studied in rats during light halothane anesthesia. Thyrotropin releasing hormone (TRH) and two TRH analogues: the desamidated form (TRH-OH) and gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN 1417) were administered intracerebroventricularly. TRH 0.5-5 micrograms induced a marked tachypnoea with a rapid onset and a duration of at least 20 min. DN 1417, a potent analogue of TRH with a very low TSH (thyroid stimulating hormone) releasing activity was more effective in stimulating respiratory frequency, while TRH-OH, regarded to have neither TSH releasing nor extra hypothalamic effects, at equimolar doses was unable to induce any changes in the respiratory pattern. When TRH was given into the fourth ventricle the dose response curve was slightly shifted to the left. In experiments employing the occluded breath technique, P0.1 was increased in the same magnitude as the mean inspiratory flow (VT/T1). The results also indicated an increase in the gain of the inflation reflex loop whereas the central bulbopontine setting for T1 and TTOT were not significantly changed. Local injection of TRH into the nucleus tractus solitarii induced a stimulation of respiratory frequency which was slower in onset compared to the response seen after injection into the lateral or fourth ventricles. Concomitantly to the respiratory changes, i.c.v. TRH injection induced a hypocarbia and an alkalosis. No changes in blood pressure or heart rate were seen. The respiratory stimulant effect of TRH could be potentiated by pretreatment with naloxone, methylatropine or a low dose of GABA. Haloperidol or propranolol did not significantly change the respiratory effects of TRH, while reserpine pretreatment seemed to blunt some of the ventilatory effects of TRH. It seems likely that TRH has few direct effects on brain stem neurones involved in the central regulation of respiration, but the main effects seem to be elicited in areas rostral to the brain stem. The respiratory stimulating effect of TRH is unrelated to TSH. Furthermore, other neurotransmitter systems might also be involved in modulation of the respiratory stimulation evoked by TRH.
在轻度氟烷麻醉下对大鼠的呼吸活动进行了研究。促甲状腺激素释放激素（TRH）和两种TRH类似物：去酰胺化形式（TRH-OH）以及γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺柠檬酸盐（DN 1417）通过脑室内注射给药。0.5 - 5微克的TRH可诱发明显的呼吸急促，起效迅速，持续时间至少20分钟。DN 1417是一种TRH的强效类似物，促甲状腺激素（TSH）释放活性非常低，在刺激呼吸频率方面更有效，而TRH-OH在等摩尔剂量下被认为既无TSH释放作用也无下丘脑外效应，无法引起呼吸模式的任何变化。当将TRH注入第四脑室时，剂量反应曲线略有左移。在采用屏气技术的实验中，P0.1的增加幅度与平均吸气流量（VT/T1）相同。结果还表明充气反射环路的增益增加，而T1和TTOT的中枢延髓桥脑设定值无显著变化。将TRH局部注射到孤束核可诱发呼吸频率的刺激，与注射到侧脑室或第四脑室后所见的反应相比，起效较慢。与呼吸变化同时发生的是，脑室内注射TRH可诱发低碳酸血症和碱中毒。未观察到血压或心率的变化。TRH的呼吸刺激作用可通过用纳洛酮、甲基阿托品或低剂量的GABA预处理来增强。氟哌啶醇或普萘洛尔未显著改变TRH的呼吸作用，而利血平预处理似乎会减弱TRH的一些通气作用。TRH似乎对参与呼吸中枢调节的脑干神经元几乎没有直接作用，但其主要作用似乎是在脑干前方的区域引发的。TRH的呼吸刺激作用与TSH无关。此外，其他神经递质系统可能也参与了对TRH诱发的呼吸刺激的调节。
