生物化学原理教学（杨荣武）Chapter17 Hormones and their receptor-mediated signal transduction.pptVIP

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生物化学原理教学（杨荣武）Chapter17 Hormones and their receptor-mediated signal transduction.ppt

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NO System Nobel Committee Says Yes to NO The discovery of NO as a signaling molecule Robert F. Furchgott, Louis J. Ignarro, Ferid Murad (1998 Nobel Laureate) Synthesis Diagram Dynamite and Angina Viagra and Impotence (Molecule of the 1992 year) Nitric oxide nitric oxide (NO) acts as a paracrine signal -only affects local area short t1/2 = 1-5 secs produced by nitric oxide synthase (NOS) from the amino acid arginine NO has role in: vasodilation of blood vessels killing of bacteria, parasites and tumours NO and vasodilation NO most potent vasodilator known produced by endothelial cells following activation by acetylcholine, GABA, adrenalin passes from endothelial cells to smooth muscles passes thu’ muscle cells via gap junctions acetylcholine, GABA, adrenalin acts as 1st messenger in endothelial cells NO acts as 1st messenger in smooth muscle cells cGMP acts as 2nd messnger Ca2+ acts as 3rd messenger Nitric oxide synthase (NOS) and the catalyzed reaction NO-mediated Vascular Relaxation Vasodilatory drugs(nitroglyerin nitrites) CH2 CH2 CH2 O NO2 O NO2 O NO2 NO is active ingredient in nitroglycerin poweful drug for heart attack and angina nitroglycerin also known as trinitroglycerin (TNT) active ingredient in dynamite Alfred Nobel invented dynamite, established Nobel Prizes with the money suffered angina and took nitroglycerin Viagra “wonderdrug” for erectile dysfunction similar mode of action as caffeine inhibits phosphodiesterase activity prevents cGMP breakdown build-up higher levels of cGMP relaxed smooth muscle increased bloodflow into corpus cavernosum erection cGMP GMP phosphodiesterase Viagra RTK System General Characteristics Closely linked to Growth factors-EGF, NGF, FGF, IGF-1, IGF-2, PDGF, CSF, Insulin et., al Receptors have intrinsic Tyrosine Protein Kinase activity (TPK) The most important pathway transmitting extracellular signals into nuclei Major players Ligands Receptors: Extracelluar domain, trans-membrane domain and intracelluar domain Ad