Lecture_13-Catecholamines

The val version results in stronger comt enzyme

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valine in the same position as the other has a methionine. The val version results in stronger COMT enzyme activity. For example, people who inherit two copies of val have 40 percent higher prefrontal cortex enzyme activity, resulting in more rapid chemical breakdown and markedly lower dopamine levels than people with two copies of met . In some studies, val has been associated with slightly increased risk for schizophrenia, but evidence now suggests that either version can potentially increase risk, depending on how prefrontal dopamine is affected by interactions with other genes and environmental events. Since people with the deletion syndrome carry only one copy of the COMT gene, their enzyme activity is already compromised. If that copy is a met , its weak enzyme action would likely expose their developing brains to excessive, potentially damaging prefrontal dopamine levels, with attendant adverse consequences, hypothesized the researchers at Stanford's Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences. Val/Val à stronger COMT activity à 40% higher breakdown Deletion syndrome: 1 copy of COMT à already compromised COMT activity - If that 1 copy contains “Met” à poorer COMT function à excessive NT levels
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Catecholamine Receptors - All DA and NE are G protein-coupled receptors - Binding site actually within the membrane - TMIII binds + charge - TM V forms hydrogen bonds
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Classification of DA receptors Classification on the basis of location, what pharmacological agents the receptors bind, and what intracellular effects ligand binding has: D1 family - Gs coupled Stimulates adenylyl cyclase D2 family - Gi coupled Inhibits adenylyl cyclase, stimulates Ca ++ influx, increases K + conductance
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Further classification of DA receptors !" #$ !" #% !( #+ !( #, !( #- #./01(2* 4*5*/6.7"
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Further classification of DA receptors
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DA: D2/D3 NE: α 2 (alpha2) Autoreceptor Inhibition
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Antipsychotic medication
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Adrenergic Receptor (AR) Intracellular Signaling - α 1 = postsynaptic - Gq = stimulatory - α 2 = presynaptic ( clonidine ) - Gi = inhibitory - β = postsynaptic - Gs = stimulatory (lungs vs. heart)
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For Review: DA DAT Inhibited by reserpine Inhibited by AMPT Inhibited by cocaine and Wellbutrin Amphetamine Antipsychotic Antipsychotic Amphetamine MAOI MAOI
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For Review: NE Inhibited by reserpine Inhibited by AMPT Clonidine is α 2 agonist MAOI
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The val version results in stronger COMT enzyme activity...

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