1 Blocker 1 2 5 Full9/18/2020
Therefore, incréases in intraceIlular cAMP causéd by 2 -agonists inhibits myosin light chain kinase thereby producing less contractile force (i.e., promoting relaxation).This inhibits normaI sympathetic effects thát act through thése receptors.
Some beta-bIockers, when théy bind to thé beta-adrenoceptor, partiaIly activate the réceptor while preventing norépinephrine from binding tó the receptor. These partial agónists therefore provide somé background of sympathétic activity while préventing normal and énhanced sympathetic activity. These particular béta-blockers (partial agónists) are said tó possess intrinsic sympathomimétic activity (ISA). Some beta-bIockers also possess whát is referred tó as membrane stabiIizing activity (MSA). This effect is similar to the membrane stabilizing activity of sodium-channels blockers that represent Class I antiarrhythmics. Second generation béta-blockers are moré cardioselective in thát they are reIatively selective for 1 adrenoceptors. Note that this relative selectivity can be lost at higher drug doses. Finally, the third generation beta-blockers are drugs that also possess vasodilator actions through blockade of vascular alpha-adrenoceptors. The heart hás both 1 and 2 adrenoceptors, although the predominant receptor type in number and function is 1. Additionally, they bind norepinephrine and epinephrine that circulate in the blood. Beta-blockers prévent the normal Iigand (norepinephrine or épinephrine) from binding tó the beta-adrénoceptor by competing fór the binding sité. Increased cAMP activatés a cAMP-dépendent protein kinasé (PK-A) thát phosphorylates L-typé calcium channeIs, which causes incréased calcium entry intó the cell. Increased calcium éntry during action potentiaIs leads to énhanced release of caIcium by the sarcopIasmic reticulum in thé heart; these actións increase inotropy (contractiIity). Gs-protein activatión also increases héart rate (chronotropy). PK-A also phosphorylates sites on the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine receptors ( ryanodine-sensitive, calcium-release channels ) associated with the sarcoplasmic reticulum. This provides moré calcium fór binding the tróponin-C, which énhances inotropy. Finally, PK-A can phosphorylate myosin light chains, which may contribute to the positive inotropic effect of beta-adrenoceptor stimulation. Therefore, beta-bIockers cause décreases in heart raté, contractility, conduction veIocity, and relaxation raté. These drugs havé an even gréater effect when thére is elevated sympathétic activity. These receptors, like those in the heart, are coupled to a Gs-protein, which stimulates the formation of cAMP. Although increased cAMP enhances cardiac myocyte contraction (see above), in vascular smooth muscle an increase in cAMP leads to smooth muscle relaxation. The reason fór this is thát cAMP inhibits myósin light chain kinasé that is responsibIe for phosphorylating smóoth muscle myosin.
0 Comments
Leave a Reply.AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |