1 / 38

The Nobel Prize in Physiology or Medicine 1998

The Nobel Prize in Physiology or Medicine 1998. "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system". Group 6 B9502002 王元欽 B9502013 吳明諴 B9502016 呂宗哲 B9502040 徐鴻麟 B9502042 屠冠翔 B9502049 莊千儀. The Introduction of Nitric oxide.

holli
Télécharger la présentation

The Nobel Prize in Physiology or Medicine 1998

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Nobel Prize in Physiology or Medicine 1998 "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system" Group 6 B9502002 王元欽 B9502013 吳明諴 B9502016 呂宗哲 B9502040 徐鴻麟 B9502042 屠冠翔 B9502049 莊千儀

  2. The Introduction of Nitric oxide

  3. NO Is Harmful to Our Body • Free radical • The combination with hemoglobin

  4. The Nobel Prize in Medicine 1998 Robert F. Furchgott

  5. Research • Factors Influencing Contractility of Cardiac Muscle • Endothelium-dependent Relaxation

  6. Discovery • EDRF(endothelium-derived relaxing factor) • Actually EDRF is NO (by 1986 Louis J. Ignarro)

  7. The paradox of ACh • 1953 paper contradictive (Reactions of strips of rabbit aorta to epinephrine, isoproterenol, sodium nitrite and other drugs) • Ach In vivorelax In vitro contract • 1980 an accidental finding (EDRF) In vitrorelax

  8. Sandwich Experiment(1980) with endothelium ‘sandwich’: ACh relaxation With no endothelium: ACh  contraction

  9. Ferid MuradThe Nobel Prize in Physiology or Medicine 1998 Discovery of Some of the Biological Effects of Nitric Oxide and Its Role in Cell Signaling

  10. The Biological Effect of NO

  11. The structure of GC （guanylyl cyclase） • Heterodimer with α and β subunits • α1, α2 , β1 andβ2

  12. NO & GC • (A) ferrous heme <--------> histidine • (B) NO binds to ferrous heme ion • (C) ferrous heme <----X----> histidine

  13. Experiment:ventilate NO into guanylyl cyclase preparations

  14. NO activate the guanylylcyclase

  15. The Nobel Prize in Medicine 1998 Louis J.Ignarro • A series of experiments were designed to test the unpublished hypothesis that EDRF might be NO

  16. First Experiment • Purpose: determine whether EDRF released from artery and vein could activate guanylate cyclase

  17. GC arterial & venous rings Procedure: acetylcholine & bradykinin methylene blue GC activated responses blocked

  18. Second Experiment • Purpose:determine whether the activation of guanylate cyclase by EDRF was heme-dependent as in enzyme activation by NO

  19. intrapulmonary arterial rings with endothelium Intrapulmonary arterial rings without endothelium Procedure and result: tissue baths tissue baths Heme-containing GC Heme-deficient GC Heme-containing GC Heme-deficient GC Ach & NO Ach & NO Ach:activity of GC NO:activity of GC  Ach:activity of GC  NO:activity of GC  Ach:activity of GC  NO:activity of GC  Ach:activity of GC  NO:activity of GC 

  20. Ignarro's spectral analysis • Hemoglobin (yellow) exposed to endothelial cells that were stimulated to produceEDRF (green) • Hemoglobin (yellow) directly exposed to NO (green)

  21. NO&cardiovascular system • NO is a signal molecule of key importance for the cardiovascular system • Known as the 'endothelium-derived relaxing factor', or 'EDRF'

  22. Function • Turns off the contraction, results in a dilatation of the arteries • Controls the blood pressure and its distribution • Prevents the formation of thrombi

  23. Production of NO • NO is biosynthesised from L-arginine and oxygen by various nitric oxide synthase (NOS) enzymes

  24. Guanylyl Cyclase (GC)

  25. The Generation of NO in Our Bodies • In synapse • In endothelium of blood vessels • In macrophages & neutrophils

  26. NOS (Notric oxide synthetase) • nNOS(neural NOS) • eNOS(endothelial NOS) • iNOS (inducible NOS)

  27. In Synapse

  28. In Macrophages & Neutrophils

  29. Viagra －against impotence • cGMP is regulated by a enzyme called PDE(Phosphodiesterase) • PDE5(type 5)will accelerate the consumption of cGMP of cavernous body of penis. As the amount of cGMP is not enough,the penis will not erect • Viagra decreases the consumption of cGMP of cavernous body of penis by inhibiting PDE5, enhancing the function of NO and making the penis erect

  30. stimulation cavernous body of penis NANC NO Endothelial cells Guanylate cyclase cGMP GTP Penile erection X GMP PDE5 Viagra

  31. Shock • Septic shock、 Hemorrhagic Shock • iNOS • excessive production of NO • Dilation of blood vessels Down of blood pressure Shock

  32. Sickle Cell Anaemia • When sickle hemoglobin (HbS) gives up its oxygen to the tissues, it sticks together to form long rods inside the red blood cells, making these cells rigid and sickle-shaped.

  33. The latest breakthrough • Discovered by Dr. C.A.Head • Result： NO will increase the affinity between hemoglobin and oxygen of patients, but no effect on normal people 「It may be one of the most important medical developments during the ten years!!」

More Related