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Neurotransmitters
Lecture 13
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 ~

Lock & Key Model
NT binds to receptor
NT = key
Receptor = lock
 Receptor changes shape
determines if EPSP or IPSP
receptor subtypes
 NOT NT ~

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 ~

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 ~

ACh - Distribution
Peripheral N.S.
 Excites somatic muscle
 Autonomic NS
 Ganglia
 Parasympathetic NS Neuroeffector
junction
 Central N.S. - widespread
 Hippocampus
 Hypothalamus ~

Excitatory Amino Acids: Glutamate
Primary NT in CNS excitatory
neurons
 Nonessential amino acids
 Synthesis
 Precursor glutamine from astroglia
 Termination
 presynaptic & glial reuptake ~

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 ~

Inhibitory Amino Acids: Glycine
Primarily spinal cord
 Cl- channels
 Strychnine is antagonist ~

Inhibitory Amino Acids: GABA
Gamma-aminobutyric acid GABAergic
 Major NT in brain inhibitory systems
 Receptor subtypes
 GABAA / GABAC ionotropic Clchannel
 GABAB - metabotropic K+ channels
 Precursor = glutamate ~

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 ~

Monamines

Catecholamines
Dopamine - DA
 Dopaminergic
Norepinephrine - NE
 Noradrenergic
Epinephrine - E
 Adrenergic
Indolamines
Serotonin - 5-HT

Serotonergic

Monamines
Terminated by...
 reuptake
 monoamine oxidase - MAO
 catechol-O-methyltranferase - COMT
 also in liver
 Reserpine  leaky vesicles
 depletes monoamines ~

Dopamine
Only in central nervous system
 mostly inhibitory systems
 Reward
 Schizophrenia
 Movement
 Nigrostriatal Pathway
 At least 5 DA-R types: D1, D2, etc. ~

Norepinephrine
Peripheral N.S.
 Sympathetic neuroeffector junction
 Adrenal glands
 Central N.S.
 Hypothalamus
 Locus coeruleus
 Alpha & Beta receptor subtypes

NEa & NEb ~

Serotonin
NOT a catecholamine
 Peripheral
 98% in blood & smooth muscle
 Central N.S.
 Raphe nucleus
 Hypothalamus
 R subtypes: 5HT1 & 5HT2 ~

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 ~

Endorphins
Opioids
 Dynorphin
 met-enkephalin
 leu-enkephalin
 Beta-endorphin
 Receptor subtypes:
 mu1, mu2, kappa, delta ~

Unconventional NTs
Retrograde messengers
++-dependent
 Ca
 Not stored in vesicles
 Nitric Oxide - It’s a gas
 Synthesis on demand by NO
synthase
 LTP ~

Unconventional NTs

Endocannabinoids
 Anandamide
 2 - AG
 Inhibits presynaptic GABA release
 Synthesis by enzymatic
degradation of membrane ~