Contractile

Microfilaments and Microtubules. There are two important classes of fibers found in the cytoplasm of many plant and animal ceUs that are characterized by nematic-like organization. These are the microfilaments and microtubules which play a central role in the determination of ceU shape, either as the dynamic element in the contractile mechanism or as the basic cytoskeleton. Microfilaments are proteinaceous bundles having diameters of 6—10 nm that are chemically similar to actin and myosin muscle ceUs. Microtubules also are formed from globular elements, but consist of hoUow tubes that are about 30 nm in diameter, uniform, and highly rigid. Both of these assemblages are found beneath the ceU membrane in a linear organization that is similar to the nematic Hquid crystal stmcture. 

Elevation of cycHc AMP levels is also known to inhibit the release of inflammatory and contractile mediators from mast cells (42). The good clinical efficacy of P2" goiAsts may be related to this action because some members of this class of dmgs inhibit mediator release at the same concentrations at which they relax smooth muscle (43). In contrast to their effectiveness against immediate bronchoconstriction, P2" gonists do not inhibit the late asthmatic... 

Muscle tissue is unique in its ability to shorten or contract. The human body has three basic types of muscle tissue histologically classified into smooth, striated, and cardiac muscle tissues. Only the striated muscle tissue is found in all skeletal muscles. The type of cells which compose the muscle tissue are known as contractile cells. They originate from mesenchymal cells which differentiate into myoblasts. Myoblasts are embryonic cells which later differentiate into contractile fiber cells. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

Bratton, D. 1.., Tanaka, D. T, and Gnmstein, M. M. (1987). Effects of temperature on cholinergic contractility of rabbit airway smooth muscle. /. Appl. Physiol. 63, 1933-1941. 

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

Picrasma crenata. Stated to contain an uncharacterised alkaloid sigmine, which lowers the contractility and tonicity of the isolated duodenal preparation of the rabbit. In dogs it is hypotensive and lowers concentration of blood sugar, 3 to 4 hours after injection. (Pereira, Ann. foe. med. Univ. S. Paulo, 1938, 14, 269 Chem. Abstr., 1939, 33, 3877).)... 

Contractile and motile proteins Actin Myosin Tubulin Dyne in Kinesin... 

Certain proteins endow cells with unique capabilities for movement. Cell division, muscle contraction, and cell motility represent some of the ways in which cells execute motion. The contractile and motile proteins underlying these motions share a common property they are filamentous or polymerize to form filaments. Examples include actin and myosin, the filamentous proteins forming the contractile systems of cells, and tubulin, the major component of microtubules (the filaments involved in the mitotic spindle of cell division as well as in flagella and cilia). Another class of proteins involved in movement includes dynein and kinesin, so-called motor proteins that drive the movement of vesicles, granules, and organelles along microtubules serving as established cytoskeletal tracks. ... 

Contractile proteins Myosin 520 43 A band Contracts with actin... 

Pyridyl-4-bromo-6-oxo-5,6,7,8-tetrahydrothiazolo[5,4-g]quinolones and analogues were prepared and tested as potential inotropic agents for treatment of heart failure. For example, the 2-(4-pyridyl) substituted thiazoloquinolone 38 gave a 122% increase in contractility of guinea pig papillary muscle (89EUP1). 

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

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