Vesicles are small and clear vesicles are docked

Info icon This preview shows pages 12–18. Sign up to view the full content.

View Full Document Right Arrow Icon
-Vesicles are small and clear - Vesicles are docked close to the active zone (i.e., require lower calcium input compared to neuropeptide-containing large, dense core vesicles) - Release occurs from varicosities along terminal = non-directional/modulatory release
Image of page 12

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Re-uptake - Plasma Membrane Transporters NET: gene found only in noradrenergic neurons DAT: gene found only in dopaminergic neurons BUT substrate specificity is lacking esp. in areas with low DAT (like PFC) where DA can be taken up by NET - 12 TM domains - Many regulatory sites - Responsible for removing 80-90% of released NT
Image of page 13
Pharmacology of Re-uptake Non-selective re-uptake inhibitors - Bind DAT, NET and SERT - Example: cocaine Selective re-uptake inhibitors - ”tri-cyclic antidepressants” can be NET only but many inhibit SERT also - Desipramine is prototypical selective NET inhibitor - Nomifensine is prototypical selective DAT inhibitor Wellbutrin/Zyban (buproprione) is antidepressant/anti-smoking drug Amphetamines (AMPHs): - Because they look like a catecholamine, AMPHs enter cell through DAT/NET - Enter through VMAT, disrupt pH of vesicle àฏ drives DA/NE out into cytosol - Increased [DA/NE] cytosol àฏ creates a concentration gradient that drives DA and NE out of the cell through DAT/NET
Image of page 14

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
1. MAO: - Monoamine oxidase oxidative deamination of catecholamines - Enzyme localized in synapse as well as in terminal (in mitochondria); cytosolic MAO responsible for majority of break-down after re- uptake DA àฏ HVA & DOPAC NE àฏ MHPG (glycol) and VMA (acid) Catecholamine metabolism 2 processes: 1. deamination 2. O-methylation 2. COMT: - Catechol-O-methyl transferase O-methylation - Breaks down small fraction of NTs in cleft - Extracellular - Principle mechanism in periphery (high MHPG in urine)
Image of page 15
Pharmacology of MAO Metabolism MAO-inhibitors (MAOI’s) “suicide substrates”; irreversible until recently - Increase NT in tissue and synapse àฏ treat OCD, depression MAO-A - Expressed almost exclusively in NE neurons - Preferential enzyme for NE, Epi and 5-HT - Binds DA with lowest affinity MAO-B - Expressed almost exclusively in 5-HT neurons, but also other monoamine neurons - May be involved in DA metabolism Genes located on X chromosome
Image of page 16

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Genetics of Metabolism: Variations in COMT A variation in the COMT gene's sequence results in two common versions: val and met — one version produces an enzyme that has the amino acid 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
Image of page 17
Image of page 18
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern