Download presentation
Presentation is loading. Please wait.
Published byElissa Cowan Modified over 9 years ago
1
The Nobel Prize in Physiology or Medicine 1998 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 "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system"
2
The Introduction of Nitric oxide
3
NO Is Harmful to Our Body Free radical The combination with hemoglobin
4
Robert F. Furchgott The Nobel Prize in Medicine 1998
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 no endothelium: ACh contraction with endothelium ‘sandwich’: ACh relaxation
10
Ferid Murad The Nobel Prize in Physiology or Medicine 1998 Discovery of Some of the Biological Effects of Nitric Oxide and Its Role in Cell Signaling
11
The Biological Effect of NO
12
The structure of GC ( guanylyl cyclase ) Heterodimer with α and β subunits α 1, α 2, β 1 and β 2
13
NO & GC (A) ferrous heme histidine (B) NO binds to ferrous heme ion (C) ferrous heme histidine
14
Experiment: ventilate NO into guanylyl cyclase preparations
15
NO activate the guanylyl cyclase
16
Louis J.Ignarro The Nobel Prize in Medicine 1998 A series of experiments were designed to test the unpublished hypothesis that EDRF might be NO unpublished hypothesis that EDRF might be NO
17
First Experiment Purpose: determine whether EDRF released from artery and vein could activate guanylate cyclase
18
Procedure:arterial & venous rings GC activated GC activated acetylcholine & bradykinin GC methylene blue responses blocked
20
Second Experiment Purpose:determine whether the activation of guanylate cyclase by EDRF was heme- dependent as in enzyme activation by NO
21
Procedure and result: intrapulmonaryarterial rings with endotheliumIntrapulmonary arterial rings without endothelium endothelium tissue baths Ach:activity of GC NO:activity of GC Ach:activity of GC NO:activity of GC Ach & NO tissue baths Ach:activity of GC NO:activity of GC Ach:activity of GC NO:activity of GC Heme-containing GC Heme-deficient GC Heme-containing GC Heme-deficient GC
23
Hemoglobin (yellow) directly exposed to NO (green) Hemoglobin (yellow) exposed to endothelial cells that were stimulated to produce EDRF (green) produce EDRF (green) Ignarro's spectral analysis
24
NO& cardiovascular system NO is a signal molecule of key importance for the cardiovascular system Known as the 'endothelium-derived relaxing factor', or 'EDRF'
25
Function Turns off the contraction, results in a dilatation of the arteries Controls the blood pressure and its distribution Prevents the formation of thrombi
26
Production of NO NO is biosynthesised from L-arginine and oxygen by various nitric oxide synthase (NOS) enzymes
28
Guanylyl Cyclase (GC)
30
The Generation of NO in Our Bodies In synapse In endothelium of blood vessels In macrophages & neutrophils
31
NOS (Notric oxide synthetase) nNOS(neural NOS) eNOS(endothelial NOS) iNOS (inducible NOS)
32
In Synapse
33
In Macrophages & Neutrophils
34
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
35
NANCNOEndothelial cells Guanylate cyclase cGM P PDE5 GTP GMP Penile erection stimulation cavernous body of penis Viagra X
36
Shock Shock Septic shock 、 Hemorrhagic Shock iNOS excessive production of NO Dilation of blood vessels Down of blood pressure Shock
37
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.
38
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 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!! 」 「 It may be one of the most important medical developments during the ten years!! 」
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.