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福司可林在体外模拟降钙素对骨吸收的作用,但不模拟甲状旁腺激素的作用。

Forskolin mimics the effects of calcitonin but not parathyroid hormone on bone resorption in vitro.

作者信息

Klein R F, Nissenson R A, Strewler G J

机构信息

Endocrine Unit, Veterans Administration Medical Center, San Francisco, CA.

出版信息

Bone Miner. 1988 Jul;4(3):247-56.

PMID:2847839
Abstract

Parathyroid hormone (PTH) and calcitonin stimulate bone adenylate cyclase activity and increase bone cAMP content, but PTH enhances and calcitonin inhibits bone resorption. This study examined the effects of forskolin, a non-hormonal activator of adenylate cyclase, on bone resorption and cAMP accumulation in 19-day fetal rat limb bones. Forskolin (10(-9) to 10(-5) M) stimulated bone cAMP generation in a concentration-dependent manner. However, in contrast to bPTH(1-34), which also stimulated cAMP accumulation, forskolin did not stimulate bone resorption. Moreover, forskolin did not augment the bone-resorbing activity of PTH even though it potentiated PTH stimulation of bone cAMP levels. Rather, high doses of forskolin (10(-6) to 10(-5) M) exhibited a calcitonin-like effect to inhibit PTH-mediated bone resorption. These results support a second-messenger function of cAMP for the inhibitory effects of calcitonin, but not for the stimulatory effects of PTH on bone resorption.

摘要

甲状旁腺激素(PTH)和降钙素可刺激骨腺苷酸环化酶活性并增加骨cAMP含量,但PTH增强而降钙素抑制骨吸收。本研究检测了腺苷酸环化酶的非激素激活剂福斯可林对19日龄胎鼠四肢骨骨吸收和cAMP积累的影响。福斯可林(10^(-9)至10^(-5) M)以浓度依赖的方式刺激骨cAMP生成。然而,与同样刺激cAMP积累的bPTH(1-34)不同,福斯可林不刺激骨吸收。此外,尽管福斯可林增强了PTH对骨cAMP水平的刺激作用,但它并未增强PTH的骨吸收活性。相反,高剂量的福斯可林(10^(-6)至10^(-5) M)表现出类似降钙素的作用,可抑制PTH介导的骨吸收。这些结果支持cAMP的第二信使功能介导降钙素的抑制作用,但不介导PTH对骨吸收的刺激作用。

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Effects of forskolin on bone in organ culture.
Am J Physiol. 1987 Jan;252(1 Pt 1):E44-8. doi: 10.1152/ajpendo.1987.252.1.E44.

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