第五章信号3 气体信号.ppt

Nitric oxide gas signals by binding directly to an enzyme inside the target cell The mechanism by which acetylcholine stimulation of the endothelial cells leads to smooth muscle relaxation also explains the mechanism of action of the chemical nitroglycerin硝酸甘油 . The drug sildenafil, sold under the trade name Viagra, is an inhibitor of a cyclic GMP-specific phosphodiesterase磷酸二酯酶 that normally catalyzes the breakdown of cyclic GMP. * Murads enzyme activation Ferid Murad knew that nitroglycerine硝化甘油caused relaxation of smooth muscle cells. The enzyme, guanylyl cyclase, was activated and increased cyclic GMP, causing relaxation of the muscle. Did nitroglycerin act via release of nitric oxide, NO? He bubbled NO-gas through tissue containing the enzyme; cyclic GMP increased! A new mode of drug action had been discovered! NO induces synthesis of cGMP by stimulation of GC leading to relaxation of myosin muscle protein Acetylcholine stimulates the endothelial cells to produce a factor, NO, which penetrates into and activates the muscle cells causing relaxation.  Two discovers: ?During the 1980s, bacteria-killing activity of macrophages in cell culture depends on the presence of arginine in the medium.?arg. is a substrate 底物, for nitric oxide synthases ?NO important biological molecule . ? It has been known for many years that acetylcholine dilate blood vessels by causing their smooth muscles to relax. In 1980, R. Furchgott NYSMC concluded that blood vessels are dilated because the endothelial cells produce a signal molecule that makes smooth muscle cells relax. In 1986 work by Furchgott and parallel work by Louis Ignarro UCLA identified NO as the signal that cause relaxation of the vascular smooth muscle. 1998, Received Nobel Prize R. Furchgott, L.Ignarro, F.Murad The action of Nitric oxide on blood vessels A signal transduction pathway that operates by means of NO and cyclic GMP that leads to the dilation of blood vessels The carbon monoxide CO acts as a