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NEUROTRANSMITTER IN SZ (DOPAMINE HYPOTHESIS (Evidence for (risk factors in…

- - - - G-protein coupled receptors
        
        alter ion channel function/ voltage gate sensor
        
        monomeric; 7 transmembrane domain; metabotropic
        
        general steps
        
        1. signaling molecule bind to receptor
        
        2. activated G protein*
        
        G protein change conformation
        
        alpha subunit dissociate with beta and gamma subunit
        
        alpha sub bind to GTP gain affinity bind to the target protein
        
        3. intrinsic GTPase hydrolyze GTP to GDP, make the alpha unit lose affinity
        
        GAP: GTPase activity protein: promote hydrolysis
        
        GTPase activity is usually low
        
        4. beta and gamma subunit rejoin the alpha subunit to return to its original conformation
        
        different types receptors
        
        beta adrenergic - NE
        
        stimualate adenylyl cyclase
        
        increase protein phosphorylation
        
        increase cAMP
        
        cAMP (step in order)
        
        second messenger
        
        cAMP is made from ATP by enzyme adenylyl cyclase
        
        cAMP is converted to AMP by enzyme phosphodiesterase
        
        AMP target protein kinase A
        
        Gs
        
        mGluR - glutamate
        
        Gq
        
        phospholipase C
        
        diacylglycerol
        
        protein kinase C
        
        Ip3
        
        Ca2+ release
        
        increase protein phosphorylation and activate calcium-binding proteins
        
        Dopamine D2 - dopamine - inhibit adenylyl cyclase
        
        decrease protein phosphorylation
        
        D1 subfamily
        
        members D1 & D5
        
        Gs
        
        increase cAMP
        
        D2 subfamily
        
        members D2, D3, D4
        
        Gi
        
        decrease cAMP
        
        3 subunits;
        
        heterotrimeric form
      - block DA receptor
    - - encode valine instead of methianine
      - COMT is responsible for degrading DA
      - decrease DA
        
        thinking: there might be compensation of DA produced