Cyclic nucleotides attenuate endothelin-1-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells
Sugimoto, T.; Kikkawa, R.; Haneda, M.; Araki, S.; Koya, D.; Togawa, M.; Shigeta, Y.
Journal of Diabetes and Its Complications 9(4): 249-251
ISSN/ISBN: 1056-8727 PMID: 8573739 DOI: 10.1016/1056-8727(95)80014-6
In order to clarify the mechanisms of interaction between endothelin-1 (ET-1) and cyclic AMP (cAMP) or cyclic GMP (cGMP), we examined the effects of cAMP or cGMP on ET-1-induced activation of mitogen-activated protein kinase (MAPK), one of the key enzymes in the signal transduction of ET-1, in cultured rat mesangial cells. ET-1 was able to activate both p42 and p44 MAP kinases in a dose-dependent manner. Cell permeable analogues of cAMP and cGMP, dibutylyl cAMP (BT2-cAMP) and 8 bromo cGMP (8br-GMP), significantly inhibited ET-1-induced activation of MAPK. Atrial natriuretic peptide (ANP), which increased cellular cGMP, was able to inhibit ET-1-induced activation of MAPK in a dose-dependent manner, while c-ANP, an analogue specific to the clearance receptors of ANP, exerted no effect. These results indicate that cAMP and cGMP could modulate the action of ET-1 in mesangial cells at a step of the activation of MAPK.