Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases D1 receptor expression in carotid bodies, PVN and striatum of hamsters.
Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases D1 receptor expression in carotid bodies, PVN and striatum of hamsters.
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DOI：
10.1016/j.brainres.2011.05.034
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发表时间：
2011-07-15
期刊：
影响因子：
2.9
通讯作者：
Schultz HD
中科院分区：
文献类型：
--
作者：
Schlenker EH;Schultz HD
甲状腺功能减退会导致呼吸困难。我们确定丙硫脲嘧啶（PTU）诱导的仓鼠甲状腺功能减退（HH）是否改变多巴胺D1受体表达、D1受体调节的通气以及缺氧或高碳血症引起的通气化学反射激活。以0.04% PTU灌胃3个月，诱导甲状腺功能减退。用生理盐水或0.25 mg/kg SCH 23390（一种D1受体拮抗剂）进行通气评估，同时清醒的仓鼠呼吸常氧（N2中含21% O2）、低氧（N2中含10% O2）和高碳酸（O2中含5% CO2）空气。与正常甲状腺仓鼠（EH）相比，HH在颈动脉体、纹状体和下丘脑室旁核中表现出D1受体蛋白水平的降低，而在孤束核中则没有。相对于EH， HH在暴露于常氧、低氧或高碳酸血症时表现出较低的通气，但对化学反射激活的通气反应性相当。SCH 23390降低暴露于常氧、低氧和高碳酸血症的EH仓鼠的通气。在HH中，SCH 23390在基线缺氧时增加通气，而在暴露于缺氧和高碳酸血症时不影响通气，导致对缺氧和高碳酸血症的化学反射激活的通气反应降低。此外，在一些脑区和颈动脉内，HH D1受体蛋白水平降低。此外，静止呼吸和气体暴露时的D1受体调节在EH中受到抑制，而在HH中没有。
Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)–induced hypothyroidism in hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for three months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390, a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2 in N2) and hypercapnic (5% CO2 in O2) air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH 23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH 23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.
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DOI：
10.1124/jpet.102.043166
发表时间：
2003-04-01
影响因子：
3.5
作者：
Liu, YX;Qin, LY;Hong, JS
通讯作者：
Hong, JS
影响因子：
4.8
作者：
Jha, A;Sharma, SK;Chaturvedi, PK
通讯作者：
Chaturvedi, PK
影响因子：
3.3
作者：
Nattie, EE;Li, AH
通讯作者：
Li, AH
影响因子：
2.9
作者：
Schlenker, E;Barnes, L;Martin, D
通讯作者：
Martin, D
影响因子：
2.9
作者：
SCHLENKER, EH;MEANS, R;BURBACH, JA
通讯作者：
BURBACH, JA