Fradkin J E, Cook G H, Kilhoffer M C, Wolff J
Endocrinology. 1982 Sep;111(3):849-56. doi: 10.1210/endo-111-3-849.
The diterpene forskolin is a potent (100-fold) stimulator of guinea pig thyroid cAMP accumulation with half-maximal activation occurring at 40 microM. Forskolin stimulation is more rapid than that of TSH, attaining a 5-fold increase within 1 min of exposure. The stimulation is also rapidly reversible. The diterpene does not sensitize thyroid cAMP accumulation to TSH, and the concentration yielding half-maximal response is not altered by the presence of low levels of forskolin. At maximally stimulating concentrations, the effects of TSH and forskolin on cAMP accumulation are additive. Forskolin stimulates thyroid adenylate cyclase approximately 10-fold in membranes from several species with half-maximal effects occurring at 3--9 microM through an action on the maximum velocity and not the Km for ATP. The activation of thyroid membranes is readily reversible. Guanyl nucleotides are not required for stimulation by forskolin, and they do not sensitize to forskolin. Moreover, the drug did not sensitize the membrane adenylate cyclase to guanosine 5'-[beta, gamma-imido]triphosphate or to isoproterenol and was equally effective with either Mg++ or Mn++ as the divalent cation. Forskolin stimulation is additive with that of guanyl nucleotides and F-. The site of action of forskolin in the adenylate cyclase complex is uncertain. Data from Bordetella pertussis, testicular, and S-49 lymphoma mutant cyclases suggest that one of the guanyl nucleotide regulatory proteins may be required to promote the forskolin effect. We conclude that forskolin is a useful activator of thyroid adenylate cyclase both in vitro and in intact tissue, which will be useful in elucidating the coupling process of the adenylate cyclase system and in differentiating cAMP-mediated from other forms of activation of the thyroid.
二萜类化合物福斯高林是豚鼠甲状腺中环磷酸腺苷（cAMP）积累的强效（100倍）刺激剂，半最大激活浓度为40微摩尔。福斯高林的刺激作用比促甲状腺激素（TSH）更快，在暴露1分钟内即可使cAMP增加5倍。这种刺激也是快速可逆的。该二萜类化合物不会使甲状腺cAMP积累对TSH敏感，且产生半最大反应的浓度不会因低水平福斯高林的存在而改变。在最大刺激浓度下，TSH和福斯高林对cAMP积累的作用是相加的。福斯高林可使几种物种的甲状腺膜中的腺苷酸环化酶活性提高约10倍，半最大效应浓度为3 - 9微摩尔，其作用机制是通过影响最大反应速度而非ATP的米氏常数（Km）。甲状腺膜的激活很容易逆转。福斯高林刺激不需要鸟苷酸，且鸟苷酸不会使甲状腺膜对福斯高林敏感。此外，该药物不会使膜腺苷酸环化酶对鸟苷5'-[β,γ-亚氨基]三磷酸或异丙肾上腺素敏感，并且以Mg++或Mn++作为二价阳离子时效果相同。福斯高林的刺激作用与鸟苷酸和F-的作用是相加的。福斯高林在腺苷酸环化酶复合物中的作用位点尚不确定。来自百日咳博德特氏菌、睾丸和S - 49淋巴瘤突变体环化酶的数据表明，可能需要一种鸟苷酸调节蛋白来促进福斯高林的作用。我们得出结论，福斯高林在体外和完整组织中都是甲状腺腺苷酸环化酶的有效激活剂，这将有助于阐明腺苷酸环化酶系统的偶联过程，并有助于区分cAMP介导的甲状腺激活与其他形式的激活。
