1. Acetylcholine & Other Neurotransmitters
Lesson 10

2. Acetylcholine - ACh Peripheral N.S. Skeletal muscle contraction
Autonomic NS
Ganglia
Parasympathetic neuroeffector junction
Central N.S. - widespread
Hippocampus
Hypothalamus ~

3. Acetylcholine - ACh AChE Receptor subtypes: 2 major groups
Nicotinic receptors - ionotropic
excitatory
Muscarinic receptors - metabotropic
excitatory or inhibitory
Degraded by acetylcholinesterase-
AChE
Membrane bound -
pre- & postsynaptic membrane -~

4. ACh Synthesis
choline
acetyltransferase
choline
+ acetyl CoA
ACh

5. Cholinergic Agonists
Direct
Muscarine
Nicotine
small doses ~

6. AChE inhibitors Physostigmine Organophosphates - irreversible DFP
Soman & Sarin
Malathion
Agonist or Antagonist?
indirect agonist ~

7. Cholinergic Antagonists
Direct
Nicotinic - Curare
Muscarinic - Atropine
Scopolamine
Indirect
Hemicholinium
Botulinus Toxin
Black Widow Spider Venom ~

8. ACh
Botulinus toxin
BWSV
AChE N M
curare
atropine

9. Excitatory Amino Acids: Glutamate
Primary NT in CNS excitatory neurons
Nonessential amino acids
Synthesis
Precursor glutamine from astroglia
Termination
presynaptic & glial reuptake ~

10. Excitatory Amino Acids: Glutamate
Receptor subtypes
Metabotropic (mGlu-R)
Inhibition of Na+ & Ca++ channels
Iononotropic: NMDA-R; AMPA-R
nonselective
Excitotoxicity
Following brain injury
Elevated Glu activity
Aspartate ~

11. Inhibitory Amino Acids: Glycine
Primarily spinal cord
Cl- channels
Strychnine is antagonist ~

12. Inhibitory Amino Acids: GABA
GABA - GABAergic
Major NT in brain inhibitory system
Receptor subtypes
GABAA - controls Cl- channel
GABAB - controls K+ channel
Degradation by GABA-T
GABA aminotransferase ~

13. GABA Synthesis Glutamine Glutamate GABA glutamate decarboxylase
glutaminase
Glutamine
Glutamate
GABA

14. GABAergic Drugs ß CCM ~ Ro 15-4513 Agonists Antagonists
Benzodiazepines
Barbiturates
Ethyl alcohol (ETOH)
Antagonists
Picrotoxin
Inverse agonist Ro
ß CCM ~

15. Neuropeptides Chains of amino acids Synthesis in soma
Often neuromodulators
Substance P - pain
Endorphins - analgesia, euphoria ~

16. Endorphins m1, m2, k, d ~ Opioids Receptor subtypes: Dynorphin
met-enkephalin
leu-enkephalin
Beta-endorphin
Receptor subtypes:
m1, m2, k, d ~
Methionine & Leucine

17. Endorphins Agonists Antagonists naloxone naltrexone ~ morphine heroin
codeine
Antagonists
naloxone
naltrexone ~

18. Some Other NTs Histamine Inflammatory Response
Nitric Oxide - It’s a gas
Retrograde messenger
Ca++-dependent
Not stored in vesicles ~

19. Some Other NTs Endocannabinoids Anandamide 2 - AG
Inhibits presynaptic GABA release
Synthesis by enzymatic degradation of membrane ~

20. Focus on
ACh NE DA
5HT
GABA
Endorphins