Neurotransmitt Glutamate
er (amino acid)
Storage Synaptic Vesicles
Synthesis Minor: alpha-ketoglutarate(from
Krebs cycle)+
NADPH/glutamate
dehydrogenase
Major: Glutamine/ glutaminase
Release Synaptic Vesicles via Ca
dependant process
VGlut moves glutamate from
cytosol to vesicle
(energy requiring)
Inhibitory by autoreceptors
(negative feedback glutamate
to inhibit glutamate release)
mGluR2 mGluR3
Inactivators Major: Uptake through plasma
membrane transporters (many
in astrocytes, few in neurons);
co transport of Na+
Glutamine-glutamate
shuttle
Glutamate accumulation
astrocyte converted to
glutamine by glutamate
synthaseglutamine released
and taken up by neuronsw/in
neurons glutamine converted to
glutamate and packaged into
vesicles
Nor epinephrine
(protype catecholamine)
Synaptic Vesicles
Regulation via Tyrosine
Hydroxylase(TH rate
limiting) cofactor
tetrahydrobiopterine BH4
Short Term: TH
phosphorylation, end
product NE inhibition of
BH4 binding
Long Term: Synthesis new
protiens (TH)
Tyrosine + Tyrosine
Hydroxylase L Dopa +
Dopa decarboxylase 
Dopamine  Dopamine B
Hydroxylase 
Norepinephrine
Release Regulated by
presynaptic receptors
(autoreceptors)
1. Ca dependant exocytosis
2. Reversal of plasma
membrane transporters
3. Dentritic release that is
no Ca dependant
Alpha2- inhibits release
Beta- increases release
1.Inactivated by diffusion
*2.Reuptake by presynaptic
neuron: neuronal not
astrocytic
-high affinity carrier
protiens selective for NT
- Energy requiring; Na co
transport
-receptor site can compete
w/drugs
-NE can be recycled or
degraded by enzymes
(intracellular)
3.Enzymatic Inactivation
MAO-monoamine ozidase
COMT- Catechol-o-methyl-
transferase
Neurotensin Anandamide
(Neuroactive (Neuroactive Lipid)
Peptide)
Dense Core Vesicles No storage, synthesized
(grannules) on demand
170 AA w 1 copy Synthesized on demand
neurotensin/ 1 copy
neuromedin Two enzyme cascade:
Precursor lipid: NAPE
(transcyclase) high
intracellular Ca required;
Phospholipase D + NAPE
anandamide and
phosphatic acid
Regulation via changes
in intracellular CA,
activity dependant,
transmitting molecule
Transported to Simultaneous w/
terminals via axonal synthesis
transport,
concentrations at
terminal are low and
can be variable;
Ca dependant;
requires high
intensity; rapid
firing of neurons to
be release
Release anywhere;
not just in the
active zone
Nonselective Enzymatic
peptidases- cleave Inactivation- FAAH-
peptide so it cant cleaves into
bind ethanolamine and
arachadonic acid
Diffusion- away from
synapose Enzyme not regulated
keeps anandamide
No reuptake by concentration low
transporters
Yet peptide can be
bound to receptor
that is internalized
Important Ionotropic- ligand gated
Receptors channels
1.Non-NMDA conduct NA/K
mostly Nadepolarization
(AMPA/kianate)
2.NMDA - conduct Ca/Na/K
HIGH CONDUCTANCE(big pipe)
Requires glycine as cofactor
and depolarization for receptor
to open
Mg plug removed w/
depolarization
Metabotropic-Gprotien
coupled receptors; mGluRs
(second messengers)
Postsynaptic-couple to ion
channels/ intracellular Ca
release via G protien
Presynaptic- G protiens to
further glutamate release
Glu receptors - asymmetrical,
on dendritic shafts and spines
Excitatory effects via
AMPA/NMDA receptos
AMPA- fast transmission to
brain Na currents (toward
threshold)
NMDA- increased intracellular
Ca rather than depolarization
(synaptic plasticity)
Overactive glutamergic
systems
Neurodegenerative
dieseases
1. AMPA lesions
2. Epilepsy/ Seizures
3.Lack O2/Glucose
excitotoxicity; ie too much
glutamate results in too much
Ca
4. Huntingtons Disease and
ALS
Other Primary excitatory NT in
mamilian brain; found all over
CNS; synapses "asymmetrical";
principle outflow neurons from
brain region are predominatley
glutamatergic
All recept. Gprotein G coupled Cannabinoid receptor
coupled CB1
-G protien coupled
Alpha 1- post synaptic- (most abundant in body)
excitatory- increase Ca - presynaptic
-inhibits opening of
Alpha 2- presynaptic- Ca channels; inhibits
inhibit adenyl cyclase NT release
Beta- bind epinephrine
better than nor
epinephrine- increase
adenylyl cyclase activity
Noradrenergic Neurons Found in prefrontal Distribution throughout
located in medulla cortex (limbic cortex) brain, highest amounts
oblongata, pons, mid brain and in the in Striatum, limbic
(Reticular Activating hypothalamus and cortex, hippocampus,
System)- arousal mid brain (co cerebellum
(conciousness) and localized w/
regulation of autonomic catecholamine Endogenous Ligand of
functions (breathing/BP) dopamine) the receptor activated by
THC
Alpha receptors - NE Co existence of
increase arousal, Neurotensin/Dopamin Brain processes: feeding,
stimulation; increase e sleep, BP, balance,
information gathering/ posture, memory,
focus (ADD) Activation of mood--modulator of
dopamine auto other NT
Beta receptors- regulation receptors (which
of sympathetic/ inhibit dopamine Activity dependant,
parasympathetic outflow, release retrograde inhibitor of
BP regulation presynaptically) NT release
actually enhance the -made when neuronal
release of neurotensin activity is high
-binds to presynaptic
terminial; inhibits Ca
influx; inhibits NT release
Increased during
stroke, seizures, brain
trauma
Many possibly
physiological roles:
obesity,
anxiety/depression; drug
abuse
CNS distribution, Peptides are co Ananadamide is N-
Physiological Roles localized w/ other NT arachadonylethanlamine
and affect and are
affected by other NT
Neurotensin
inactivation/ sucretion
is more haphazard
than other NT glu/NE