more on GPCRs

more on GPCRs

1. GPCRs consist of

   • GPCR receptor protein itself
   • G protein - heterotrimeric: alpha binds to GTP when active and hydrolyses to GDP to stop signalling
   • effector proteins
     • ie enzymes and ion channels

2. wy do we need GPCRS

   • they allow conserved signalling machinery to generate complex responses
     • amplification
       • one receptor may activate many g proteins
       • one g protein may activate many effectors
     • diersityy
       • a single receptor may activate different g protein classes which have different signal properties
       • a single g protein may activate different effectors
       • g protein subunits alpha and beta game may activate different effectors

3. heterotrimeric g proteins are grouped into three primary classes based on they downstream signalling properties

   • Gs familly
     • acticates addrenylate cyclase to increase cAMP
     • example
       • beta- adrenoreceptor
         • two types of these mediate the effects of epinephrine
         • effect of increases cAMP
           • beta 1: increases heart rate and force of heart beat
           • beta 2: relaes bronchial smooth muscle
         • clinical pharmacology of beta adrenoreceptors
           • agonists in the lunge salbutamol (b2 selective)
             • dilates bronchial smooth muscle
             • eases respiration
             • used in asthma
           • antagonists in the heart
             • eg atenol: b1 selective
               • compettetive reversible ntagonist
               • slows heart rate and reduces force of beat
               • used in cardiovascular disease i.e. hypertension
   • Gi familly
     • inhibits adrenylae cyclase to decrease cAMP
   • GQ familly
     • ativates phospholipase C to produce IP3 and DAG
     • activation leads to activation of protein kinase C
     • example: alpha adrenoreceptor
       • activated by epinephrine
       • expressed in smooth muscle
       • Couples to Gq protein! • Activates PLC to Generate IP3 and DAG"
       • Increases intracellular Ca2+ concentration! • release from SR (IP3) and " • through membrane channels (DAG
         • Ca2+ stimulates smooth muscle conttaction
       • clinical pharmacology of alpha 1 adrenoreceptor
         • Prazosin – competitive reversible antagonist of the α1-adrenoceptor
         • prevents contraction in blood vessel walls hence blood vessel dilate and press falls
         • used in cardiovascular disease i.e. hypertension