1. Neurotransmitters
Lecture 13

2. CRITERIA NT found in axon terminals NT released by action potentials
Synthesis identified
External application mimic normal Response
Pharmacology same for normal and externally applied NT ~

3. Lock & Key Model NT binds to receptor NT = key Receptor = lock
Receptor changes shape
determines if EPSP or IPSP
receptor subtypes
NOT NT ~

4. Structure-activity relationship
NT fits receptor site
key & lock
Change structure of drug...
change its affinity
increase or decrease
may bind to different receptor
Behavior mediated by synaptic activity
most drugs act at synapse ~

5. Acetylcholine - ACh Most abundant NT in Peripheral N.S.
also found in Central N.S.
Precursor = choline
Degraded by acetylcholinesterase-
AChE
Nicotinic receptor – ionotropic
*Nonselective ionophores
*Requires 2 Ach for activation
Muscarinic receptor - metabotropic ~

6. ACh - Distribution Peripheral N.S. Excites somatic muscle Autonomic NS
Ganglia
Parasympathetic NS Neuroeffector junction
Central N.S. - widespread
Hippocampus
Hypothalamus ~

7. ACh A
Botulinum toxin
BWSV
curare atropine
AChE
AChE N M

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

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

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

11. Inhibitory Amino Acids: GABA
Gamma-aminobutyric acid - GABAergic
Major NT in brain inhibitory systems
Receptor subtypes
GABAA / GABAC ionotropic Cl- channel
GABAB - metabotropic K+ channels
Precursor = glutamate ~

12. Biogenic Amines (Monamines)
Amino acid precursors
single amine group
2 groups
Catecholamines - catechol ring
Tyrosine precursor
Indolamine - indole ring
Tryptophan precursor
Affected by many of same drugs ~

13. Monamines Catecholamines Dopamine - DA Dopaminergic
Norepinephrine - NE
Noradrenergic
Epinephrine - E
Adrenergic
Indolamines
Serotonin - 5-HT
Serotonergic

14. Monamines Terminated by... reuptake monoamine oxidase - MAO
catechol-O-methyltranferase - COMT
also in liver
Reserpine  leaky vesicles
depletes monoamines ~

15. Monoamines
MAO
Reserpine A
COMT
MAO

16. Dopamine Only in central nervous system mostly inhibitory systems
Reward
Schizophrenia
Movement
Nigrostriatal Pathway
At least 5 DA-R types: D1, D2, etc. ~

17. Norepinephrine Peripheral N.S. Sympathetic neuroeffector junction
Adrenal glands
Central N.S.
Hypothalamus
Locus coeruleus
Alpha & Beta receptor subtypes
NEa & NEb ~

18. Serotonin NOT a catecholamine Peripheral 98% in blood & smooth muscle
Central N.S.
Raphe nucleus
Hypothalamus
R subtypes: 5HT1 & 5HT2 ~

19. Neuropeptide Chains of amino acids Synthesis in soma
Often neuromodulators
alters sensitivity of neurons
slower, longer-lasting effects
Substance P - pain signaling
Endorphins - analgesia, euphoria ~

20. Endorphins Opioids Dynorphin met-enkephalin leu-enkephalin
Beta-endorphin
Receptor subtypes:
mu1, mu2, kappa, delta ~

21. Unconventional NTs Retrograde messengers Ca++-dependent
Not stored in vesicles
Nitric Oxide - It’s a gas
Synthesis on demand by NO synthase
LTP ~

22. Unconventional NTs Endocannabinoids Anandamide 2 - AG
Inhibits presynaptic GABA release
Synthesis by enzymatic degradation of membrane ~