Daza F J, Parrilla R, Martín-Requero A
Department of Physiopathology and Human Molecular Genetics, Centro de Investigaciones Biológicas, Madrid, Spain.
Am J Physiol. 1997 Dec;273(6):E1065-72. doi: 10.1152/ajpendo.1997.273.6.E1065.
The present work aimed to elucidate the influence of thyroid functional status on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrecirculating liver perfusion system featuring continuous monitoring of portal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyroid, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the alpha 1-adrenergic stimulation of respiration, glycogen breakdown, and gluconeogenesis. These effects were accompanied by a decreased intracellular Ca2+ mobilization corroborating that those processes are regulated by the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway. Moreover, in hyperthyroid rats the alpha 1-adrenergic-induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neither the alpha 1-adrenergic stimulation of vascular smooth muscle contraction nor the alpha 1-agonist-induced intracellular alkalinization and protein kinase C (PKC) activation. Thus the distinct impairment of the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway by thyroid status provides a useful tool to investigate the role played by each signaling pathway, Ca2+ or PKC, in controlling hepatic functions.
本研究旨在阐明甲状腺功能状态对α1 - 肾上腺素能受体诱导的肝脏代谢功能激活的影响。实验在非循环肝脏灌注系统中进行，该系统可连续监测门静脉压力、PO2、pCa和pH，或使用来自甲状腺功能正常、甲状腺功能亢进和甲状腺功能减退大鼠的分离肝细胞。甲状腺功能减退会降低α1 - 肾上腺素能对呼吸、糖原分解和糖异生的刺激作用。这些作用伴随着细胞内Ca2 +动员的减少，这证实了这些过程受α1 - 肾上腺素能受体信号通路中Ca(2 +)依赖分支的调节。此外，在甲状腺功能亢进的大鼠中，α1 - 肾上腺素能诱导的胞质Ca2 +增加增强，而葡萄糖合成或动员未改变。甲状腺状态既不影响α1 - 肾上腺素能对血管平滑肌收缩的刺激，也不影响α1 - 激动剂诱导的细胞内碱化和蛋白激酶C（PKC）激活。因此，甲状腺状态对α1 - 肾上腺素能受体信号通路中Ca(2 +)依赖分支的明显损害为研究Ca2 +或PKC每条信号通路在控制肝脏功能中所起的作用提供了一个有用的工具。
