一种福斯可林衍生物，盐酸可乐福可，通过环磷酸腺苷途径抑制大鼠系膜细胞有丝分裂。

A forskolin derivative, colforsin daropate hydrochloride, inhibits rat mesangial cell mitogenesis via the cyclic AMP pathway.

作者信息

Ogata Junichi, Minami Kouichiro, Segawa Kayoko, Yamamoto Chieko, Kim Sung-Teh, Shigematsu Akio

机构信息

Department of Anesthesiology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.

出版信息

Pharmacology. 2003 Nov;69(3):127-31. doi: 10.1159/000072664.

DOI:10.1159/000072664

PMID:14512698

Abstract

A forskolin derivative, colforsin daropate hydrochloride (CDH), has been introduced as an inotropic agent that acts directly on adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels and ventricular contractility, resulting in positive inotropic activity. We investigated the effects of CDH on rat mesangial cell (MC) proliferation. CDH (10(-7)-10(-5) mol/l) inhibited [(3)H]thymidine incorporation into cultured rat MCs in a concentration-dependent manner. CDH (10(-7)-10(-5) mol/l) also decreased cell numbers in a similar manner, and stimulated cAMP accumulation in MCs in a concentration-dependent manner. A protein kinase A inhibitor, H-89, abolished the inhibitory effects of CDH on MC mitogenesis. These findings suggest that CDH would inhibit the proliferation of rat MCs via the cAMP pathway.

摘要

一种福斯可林衍生物，盐酸可乐福司（CDH），已作为一种正性肌力药物被引入，它直接作用于腺苷酸环化酶以提高细胞内环磷酸腺苷（cAMP）水平和心室收缩力，从而产生正性肌力活性。我们研究了CDH对大鼠系膜细胞（MC）增殖的影响。CDH（10⁻⁷ - 10⁻⁵ mol/L）以浓度依赖性方式抑制[³H]胸苷掺入培养的大鼠MCs中。CDH（10⁻⁷ - 10⁻⁵ mol/L）也以类似方式减少细胞数量，并以浓度依赖性方式刺激MCs中的cAMP积累。蛋白激酶A抑制剂H - 89消除了CDH对MC有丝分裂的抑制作用。这些发现表明CDH将通过cAMP途径抑制大鼠MCs的增殖。