Norepinephrine origins pons and medulla a6a4 locus

Info icon This preview shows pages 4–13. Sign up to view the full content.

View Full Document Right Arrow Icon
Norepinephrine Origins: Pons and medulla A6/A4: Locus coeruleus + caudal extension A5/A7: Lateral tegmental area A2: dorsal medullary group DA - Dopamine A10: substantia nigra pars compacta (SNc) - Nigrostriatal pathway A9: ventral tegmental area (VTA) Arcuate nucleus (hypothalamus) Mesolimbic dopamine pathway Relatively discrete projections of the major catecholamine pathways in the brain
Image of page 4

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

View Full Document Right Arrow Icon
What are Catecholamines ? Molecules with a catechol nucleus and an ethylamine group attached in position 1 All are synthesized from a common pathway originating from tyrosine (dietary essential amino acid) Tyrosine is actively transported across BBB
Image of page 5
TH - requires tetrhydrobiopterin (hydrogen donor) - rate-limiting enzyme that is inhibited by AMPT AADC - Localized to dopamine neurons (formerly dopamine decarboxylase) - Fast-acting enzyme - Requires pyridoxal phosphate (from vitamin B6) as a cofactor DBH - Localized to NE neurons (of brain and sympathetic nervous system) - Requires vitamin C as a cofactor PNMT - Localized to adrenergic neurons and adrenal medulla * Tyrosine is typically saturated
Image of page 6

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

View Full Document Right Arrow Icon
Catecholamine Pathway Simplified Tyrosine Dopa Dopamine Norepinephrine Epinephrine TH AADC DBH PNMT
Image of page 7
Short-Term Regulation of TH End-product enzyme inhibition (ie. DOPA inhibits TH) Regulated at the transcriptional, translational and post- translation levels Rapid, short-term regulation Phosphorylation and dephosphorylation at 4 key serine residues Phosphorylation induces a conformational change in enzyme that increases affinity for co-factor and reduces affinity of catecholamine (reduces end-product feedback) increase in catalytic activity increase in DA, NE and Epi
Image of page 8

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

View Full Document Right Arrow Icon
Long-Term Regulation of TH Longer term regulation occurs through transcriptional regulation of the TH gene TH promoter contains several regulatory elements including: CRE, GRE, AP-1 CRE appears to be critical for chronic up-regulation of gene transcription
Image of page 9
Catecholamine Storage Vesicular storage H + ATP-ase & VMAT (vesicular monoamine transporter) mediate vesicular packaging VMAT blocked by reserpine ; causes temporary increase in cytosolic neurotransmitter levels followed by a decrease in NT packaged in vesicles --> no vesicular DA released upon AP
Image of page 10

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

View Full Document Right Arrow Icon
NE Storage -in NE neurons , vesicles also contain DBH to convert DA to NE -in blocking DA uptake into vesicles, reserpine also reduces NE levels - Amphetamines enter through VMAT, disrupt pH of vesicle àฏ drives DA/NE out into cytosol
Image of page 11
Storage/Release: -Vesicular = exocytosis
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
Image of page 13
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