Brown J W, Sirlin E A, Benoit A M, Hoffman J M, Darnall R A
Department of Physiology, Dartmouth Medical School, One Medical Center Dr., Borwell Bldg., Lebanon, NH 03756, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R884-94. doi: 10.1152/ajpregu.00655.2007. Epub 2007 Dec 19.
Activation of 5-HT1A receptors in the medullary raphé decreases sympathetically mediated brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction when previously activated with leptin, LPS, prostaglandins, or cooling. It is not known whether shivering is also modulated by medullary raphé 5-HT1A receptors. We previously showed in conscious piglets that activation of 5-HT1A receptors with (+/-)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the raphé that contains substantial numbers of 5-HT neurons, eliminates rapid eye movement (REM) sleep and decreases shivering in a cold environment, but does not attenuate peripheral vasoconstriction. Hoffman JM, Brown JW, Sirlin EA, Benoit AM, Gill WH, Harris MB, Darnall RA. Am J Physiol Regul Integr Comp Physiol 293: R518-R527, 2007. We hypothesized that, during cooling, activation of 5-HT1A receptors in the medullary raphé would also eliminate REM sleep and, in contrast to activation of 5-HT1A receptors in the PGCL, would attenuate both shivering and peripheral vasoconstriction. In a continuously cool environment, dialysis of 8-OH-DPAT into the medullary raphé resulted in alternating brief periods of non-REM sleep and wakefulness and eliminated REM sleep, as observed when 8-OH-DPAT is dialyzed into the PGCL. Moreover, both shivering and peripheral vasoconstriction were significantly attenuated after 8-OH-DPAT dialysis into the medullary raphé. The effects of 8-OH-DPAT were prevented after dialysis of the selective 5-HT1A receptor antagonist WAY-100635. We conclude that, during cooling, exogenous activation of 5-HT1A receptors in the medullary raphé decreases both shivering and peripheral vasoconstriction. Our data are consistent with the hypothesis that neurons expressing 5-HT1A receptors in the medullary raphé facilitate spinal motor circuits involved in shivering, as well as sympathetic stimulation of other thermoregulatory effector mechanisms.
当先前用瘦素、脂多糖、前列腺素或降温激活时，延髓中缝核5-HT1A受体的激活会降低交感神经介导的棕色脂肪组织（BAT）产热和外周血管收缩。尚不清楚颤抖是否也受延髓中缝核5-HT1A受体的调节。我们之前在清醒仔猪中发现，用（±）-8-羟基-2-（二丙基氨基）-四氢萘（8-OH-DPAT）激活中缝外侧巨细胞旁核（PGCL，中缝外侧的一个延髓区域，含有大量5-HT能神经元）中的5-HT1A受体，会消除快速眼动（REM）睡眠，并减少寒冷环境中的颤抖，但不会减弱外周血管收缩。Hoffman JM、Brown JW、Sirlin EA、Benoit AM、Gill WH、Harris MB、Darnall RA。《美国生理学杂志：调节、整合与比较生理学》293：R518-R527，2007年。我们假设，在降温过程中，延髓中缝核中5-HT1A受体的激活也会消除REM睡眠；与PGCL中5-HT1A受体的激活相反，会减弱颤抖和外周血管收缩。在持续凉爽的环境中，将8-OH-DPAT透析到延髓中缝核中会导致非快速眼动睡眠和清醒状态交替出现的短暂时期，并消除REM睡眠，这与将8-OH-DPAT透析到PGCL中时观察到的情况相同。此外，在将8-OH-DPAT透析到延髓中缝核后，颤抖和外周血管收缩均显著减弱。在透析选择性5-HT1A受体拮抗剂WAY-100635后，8-OH-DPAT的作用被阻断。我们得出结论，在降温过程中，延髓中缝核中5-HT1A受体的外源性激活会减弱颤抖和外周血管收缩。我们的数据与以下假设一致：在延髓中缝核中表达5-HT1A受体的神经元促进参与颤抖的脊髓运动回路，以及对其他体温调节效应机制的交感神经刺激。
