福司可林刺激人结肠隐窝中的腺苷酸环化酶：与血管活性肠肽的相互作用。

Forskolin stimulates adenylate cyclase in human colonic crypts: interaction with VIP.

作者信息

Boige N, Amiranoff B, Munck A, Laburthe M

出版信息

Eur J Pharmacol. 1984 May 18;101(1-2):111-7. doi: 10.1016/0014-2999(84)90036-0.

Abstract

Forskolin in the 10(-8)-10(-4) M concentration range (ED50 2 microM) strongly stimulated the cyclic AMP production of epithelial crypts isolated from the human colon. At a maximal dose, production increased up to 500 and 700 times the basal cyclic AMP levels at 15 and 37 degrees C, respectively. Forskolin was thus much more efficient than VIP, which is the physiological regulator of this system. Forskolin (ED50 7 microM) also stimulated colonic membrane adenylate cyclase. The stimulation was immediate, did not require guanyl nucleotides and was inhibited by calcium (10(-5)-10(-3) M). In the concentration range between 10(-9) and 10(-5) M (ED50 0.04 microM), forskolin strongly potentiated the stimulation of adenylate cyclase by VIP. We conclude that: (1) forskolin exerts a double dose-dependent action on cyclic AMP production in human colonic crypts, i.e. direct activation of basal adenylate cyclase activity and potentiation of VIP effect; (2) forskolin may be a unique pharmacological tool to investigate the cyclic AMP-dependent processes in human intestine.

摘要

浓度在10⁻⁸ - 10⁻⁴ M范围内的福斯可林（半数有效剂量为2 μM）强烈刺激了从人结肠分离出的上皮隐窝中环状AMP的生成。在最大剂量下，15℃和37℃时，生成量分别增加至基础环状AMP水平的500倍和700倍。因此，福斯可林比该系统的生理调节因子血管活性肠肽（VIP）更有效。福斯可林（半数有效剂量为7 μM）也刺激结肠膜腺苷酸环化酶。这种刺激是即时的，不需要鸟苷酸，并且受到钙（10⁻⁵ - 10⁻³ M）的抑制。在10⁻⁹至10⁻⁵ M的浓度范围内（半数有效剂量为0.04 μM），福斯可林强烈增强了VIP对腺苷酸环化酶的刺激作用。我们得出以下结论：（1）福斯可林对人结肠隐窝中环状AMP的生成具有双重剂量依赖性作用，即直接激活基础腺苷酸环化酶活性并增强VIP的作用；（2）福斯可林可能是研究人肠道中环状AMP依赖性过程的独特药理学工具。