Beta Blockers Absorptionβ-受体阻断剂的吸收.pptVIP

Beta-blockers work by competitively binding to the beta receptors blocking the binding of catecholamines like epinephrine. * The Beta receptor structure contains 7 tm helices and is coupled with G proteins. There are 2 types: beta 1 which is found in the brain and heart and beta 2 which is found in the heart, lungs and other tissues * This is the EN Signalling pathway.The G protein consists of alpha, beta and gamma subunits and in its inactive form GDP is bound to the alpha subunit. The symNS releases epinephrine which acts as a ligand and binds to the receptor causing a conformational change where GDP and the beta-gamma subunits dissociate GTP then binds to the remaining alpha subunit. This complex activates adenylate cyclase which converts ATP into cAMP. cAMP then activates PKA which phosphorylates many protein targets. * Here is a list of potential effects that can occur via the cAMP pathway. For example, muscle contraction and the opening of chloride channels can be stimualted. * The cAMP pathway is the same as discussed so here we will focus on PKA’s effects on intracellular calcium levels. PKA phosphorylation stimulates: Calcium influx through calcium channels, calcium release by the sacroplasmic reticulum and phosphorylates troponin . All these changes allow for muscle contraction in the heart * In the smooth muscle, PKA effects are opposite to that of what happens in the cardiac muscle. Calcium efflux by calcium channels, calcium uptake by SR and decreases in actin-myosin interactions These all facilitate muscle relaxation * BETA BLOCKERS Course: PHM 142 Term: Fall 2012 Group Members: Gary Lam, Matthew Pak, and Kang Hai Chen PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson DISCOVERY Discovered by James W Black in 1962 Propanolol and Pronethalol are the first clinically significant beta blockers Used for angina pectoris - chest pain from restricted blood flow to heart WHAT ARE BETA BLOCKERS Normally, catecholamines bind beta rece