Lecture 6 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Includes neurotransmitter release, reuptake, and inactivation

1. Neurocommunication
Brian J. Piper, Ph.D.

2. Terminology
• Neurotransmitter: chemical that is released in
the brain and has an effect on a local target
• Hormone: chemical that is released into
bloodstream that has an effect on a distant
target

3. Goals
• Neurotransmission
– History
– Onset: Neurotransmitter release (classical and
non-classical)
– Offset: autoreceptors, transporters, enzymes
– Receptor Families
• Endocrine

4. History: Golgi vs. Cajal
• Italian physician
• Reticulum theory
• Silver stain
Camillo Golgi (1843-1926)

5. Controversy: Golgi vs. Cajal
• Santiogo Ramon y Cajal
– Neuroanatomist
– Used Golgi’s technique
– Neuron theory
1852-1934
Chicken cerebellum

6. Neural Communication
The body’s information system is built from
billions of interconnected cells called neurons.
Communication between neurons is both
electrical and chemical.

7. Otto Loewi
• Discovered “Vagusstoff” later
known as acetylcholine
• “father of neuroscience”
• Nobel Prize 1936

8. What are amino acids?
• Amine (NH2) + Carboxyl ( -COOH)
• 20 total, 9 essential
tyrosine Tryptophan

9. More terminology
• Peptides: short (<50) strings of amino acids,
Valine-Glycine-Serine-Alanine… e.g. NPY
C terminal: COOH
N terminal: NH2
Arginine, Proline, Lysine, Phenylalanine,
Methionine, Histidine, Aspartic Acid, Valine

10. More terminology
• Peptides: short (<50) strings of amino acids,
Valine-Glycine-Serine-Alanine… e.g. NPY

11. More terminology
Proteins: longer strings of amino acids, have 3-D
structure, form receptors, transporters

12. Comparison
Peptide Protein
Size (amino acids) < 40 >40
Dimensions 1-D 3-D
Complexity Low High
Hemoglobin

13. “Typical” Synapse

14. Electron Microscope
• Beams of electrons are presented to a thin
section, 50 pm (10-12) resolution
• Reveals different types of Synapses

15. Dendritic Spine

16. Axodendritic Synapse

17. Axosomatic Synapse

18. Neurotransmitter Criteria
• 1) Found and made presynaptically.
• 2) Mechanism for inactivation.
• 3) Stimulating neuron releases it.
• 4) Receptors found postsynaptically.
• 5) Applying substance has biological effect.
• 6) Antagonizing inhibits biological effect.
“neuromodulators”

19. Neurotransmitter Comparison
Classical Non-Classical
Discovery 1950’s 1980’s
Concentration High Low
# Few Many
Synthesis Anywhere Soma

20. Classical Neurotransmitters
• Monoamines: dopamine, norepinephrine,
serotonin
• Acetylcholine (ACh)
• Amino Acids: glycine, GABA, Glutamate

21. Non-classical Neurotransmitters
• Peptides: Corticotropin-releasing factor (CRF),
endorphins
• Lipids: Anandamide
• Gases: Nitric Oxide

22. Co-Transmitters
Amine/Amino Acid Peptide
Dopamine Cholecystokinin (CCK)
Norepinephrine enkephalin
Epinephrine neurotensin
Serotonin substance P
Acetylcholine somatostatin
Gamma aminobutyric acid (GABA) motilin
Stahl, S. (2000). Essential Psychopharmacology, p. 20.

23. Axon Terminal

24. Brakes II
• Autoreceptors: this receptor (“auto” = “self”)
can act to inhibit further neurotransmitter
release
– Terminal (axon) autoreceptors: inhibit
neurotransmitter release
– Somatodendritic autoreceptors: reduce rate of
action potentials

25. Brakes I
• Enzyme: A + B __ENZ____> AB
• Enzyme: CD __ENZ____> C + D

26. Transporters
• Proteins that move molecule from one place
to another, examples:
– SERT: serotonin transporter
– NET: norepinephrine transporter
– DAT: dopamine transporter
Inside
----------------------------------------------------------------------
Outside

28. Post-synaptic
• Ligand: substance that binds to a receptor
• Ion: atom where # electrons ≠ # protons
– Ca2+ Na+ K+
– Cl-
• First messenger: neurotransmitter
• Second messenger: other molecule
• Kinase: enzyme that adds phosphate (PO4)

29. Types of Receptors

30. So Many Receptors!
Serotonin (5-HT):
1
2
3
4
5
6
7

31. Family 1: Ionotropic
• Binding to receptor opens channel to let ions
in (aka: ligand gated ion receptors)

32. Family 1: Ionotropic
• Binding to receptor opens channel to let ions
in (aka: ligand gated ion receptors)
0:40 – 6:20: http://www.youtube.com/watch?v=8jPH2pKzIDY

33. Family 2: Metabotropic (2nd messenger)
• Steps:
• 1) Ligand binds receptor
• 2) G protein acts on enzyme
• 3) Enzyme regulates 2nd
messenger
• 4) 2nd messenger acts on
protein kinase
6:30-9:00 http://www.youtube.com/watch?v=8jPH2pKzIDY

34. Family 2: Metabotropic (Channel)
• Steps:
• 1) Ligand binds receptor
• 2) G protein alters
channel
• 3) ions flow out of
neuron

35. Receptor Families Compared
Ionotropic Metabotropic
Subunits 4-5 1
Mechanism Simple: Channel opening Complex: G protein cascade
2nd messengers No Yes
Speed Fast Slow
Meyer & Quenzer (2005). p 73

36. Family 3: Tyrosine Kinase
• Steps:
1) Ligand (BDNF) binds to Trk receptor
2) Trk receptors come together, and
phosphorylate each other

38. So many drug targets!!!
Examples:
1) Tryptophan
6) Nicotine
10) MAO-I
11) SSRIs

39. Endocrine System
Gland Hormone (Function)
Pineal Melatonin (light-dark rhythm)
Thyroid T3/T4 (energy)
Adrenal Cortisol (stress)
Pancreas Insulin (glucose)
Ovaries Estrogens (2nd sex characteristics)
Testes Androgens (2nd sex characteristics)

40. Example
• Rats that received ecstasy (MDMA) during
adolescence were more sensitive to a 5-HT2
agonist when adults
Biezonski et al. (2009). Brain Research, 1252, 87-93.

41. Reference