Muscle proposed mechanisms

Pig. 2. Proposed mechanism of inbition of smooth muscle contraction by P2" gonists, where AMP is adenosine monophosphate, cAMP is cycHc-3 5 adenosine monophosphate, ATP is adenosine triphosphate, and -P is an attached phosphate. 

Huxley, A.F., Simmons, R. Proposed mechanism of force generation in striated muscle. Nature 233 533-538, 1971. 

Theophylline, a dimethylxanthine, causes broncho-dilation, possibly by inhibiting the enzyme phosphodiesterase in smooth muscle of the bronchioli. An other proposed mechanism of action is that of adenosine receptor antagonism. It has positive chronotropic and inotropic, CNS stimulant and weak diuretic properties. In obstructive lung disease sustained release tablets are to be preferred. Theophy-line has a narrow therapeutic index. Therapeutic plasma concentrations are between 7-15 mg/1. Theophylline undergoes N-demethylation via CYPl A2 in the liver and is eliminated in the urine as metabolites... 

Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol (endothelium-derived releasing factor, or EDRF). EDRF activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation. SH, sulfhydryl. 

Another proposed mechanism is inhibition of cell-surface receptors for adenosine. These receptors modulate adenylyl cyclase activity, and adenosine has been shown to provoke contraction of isolated airway smooth muscle and histamine release from airway mast cells. It has been shown, however, that xanthine derivatives devoid of adenosine antagonism (eg, enprofylline) may be potent in inhibiting bronchoconstriction in asthmatic subjects. 

Fig. 29.2 PeptoPro for faster muscle refueling. Proposed mechanism.

Hydralazine causes direct relaxation of arteriolar smooth muscle. The arteriolar vasodilatation produced by hydralazine requires an intact endothelium. Therefore, one proposed mechanism of action is that hydralazine liberates nitric oxide from the endothelium (similar to the nitrates), which in turn increases cGMP to ultimately prevent the phosphorylation of myosin light chain (which is required for smooth muscle contraction) resulting in arteriolar vasorelaxation. 

Fig. 10.6 Schematic diagram of proposed mechanisms by which NO-containing molecules relax vascular smooth muscle (redrawn and modified after Van de Voorde 1991 [7]). NTG, nitroglycerin R-0-N02, organic nitrate ISDN, isosorbide dinitrate ISMN, isosorbide mononitrate R -SH and R"-SH, thiol-containing molecules R -S-S-R disulfides R-OH,...

How does cGMP bring about relaxation of vascular smooth muscle Several mechanisms, all of which involve PKG, have been proposed none of them is at present certain to be the major one. Moreover, while several relevant changes in protein phosphorylation have been observed, it is not clear at present whether they are caused by PKG directly or by intervening secondary kinases. 

The inhalational anesthetics halothane, isoflurane, and enflu-rane all have been reported to have a positive effect in children and adults with severe asthma that is unresponsive to standard medical therapy. The proposed mechanisms for inhalational anesthetics include direct action on bronchial smooth muscle, inhibition of airway reflexes, attenuation of histamine-induced bronchospasm, and interaction with /32-adrenergic receptors. Well-controlled trials with these agents have not been completed. Potential adverse effects include myocardial depression, vasodilation, arrhythmias, and depression of mucociliary function. In addition, the practical problem of delivery and scavenging these agents in the intensive care environment as opposed to the operating room is a concern. The use of volatile anesthetics cannot be recommended based on insufficient evidence of efficacy. 

Proposed Mechanisms and Sight of Action of Calcium Inhibitory Compounds in Cardiac Muscle... 

Fig- (8). Proposed Mechanisms Underlying the Smooth Muscle Relaxation EfTecl orButylidenephthalide (20)... 

FIG. 3. Proposed mechanism for muscle bundle disintegration during tumbling and drying. Simultaneous application of tumbling and heat creates shear forces and drives off moisture causing the muscles to separate into smaller bundles. Source Chang et at. (1991). Reprinted with kind permission from Elsevier Science Ltd. 

C. Chronic repeated dosing. The emetine component causes inhibition of protein synthesis that is particularly demonstrated in human myocytes and skeletal muscle cells after overdose or prolonged use. Another proposed mechanism for cellular toxicity includes blockade of sodium and calcium channels. 

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals. The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells positively correlates with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected. An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which the decrease in white blood cells is chiefly neutrophils) is unknown. Proposed mechanisms to account for neutropenia from copper deficiency include (1) early desttuction of bone marrow progenitor cells (2) impaired synthesis of neutrophils from progenitor cells ... 

Some birds may not die immediately after drinking lethal cyanide solutions. Sodium cyanide rapidly forms free cyanide in the avian digestive tract (pH 1.3-6.5), whereas formation of free cyanide from metal cyanide complexes is comparatively slow. A high rate of cyanide absorption is critical to acute toxicity, and absorption may be retarded by the lower dissociation rates of metal-cyanide complexes. In Arizona, a red-breasted merganser (Mergus senator) was found dead 20 km from the nearest known source of cyanide, and its pectoral muscle tissue tested positive for cyanide. A proposed mechanism to account for this phenomenon involves weak-acid dissociable (WAD) cyanide compounds. Cyanide bound to certain metals, usually copper, is dissociable in weak acids such as stomach acids. It has been suggested that drinking of lethal cyanide solutions by animals may not result in immediate death if the cyanide level is... 

Chapter 14 shows how modeling can propose mechanisms to explain experimentally observed oscillations in the cardiovascular system. A control system characterized by a slow and delayed change in resistance due to smooth muscle activity is presented. Experiments on this model show oscillations in the input impedance frequency spectrum, and flow and pressure transient responses to step inputs consistent with experimental observations. This autoregulation model supports the theory that low-frequency oscillations in heart rate and blood pressure variability spectra (Mayer waves) find their origin in the intrinsic delay of flow regulation. 

Drawing illustrating the proposed mechanism of conversion of a pleated sheet into a double row of 3.7-residue helixes this is proposed as the process involved in the contraction of muscle. 

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