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Non-classical neurotransmitters
Nitric Oxide
PeptidesATP and Adenosine
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Nitric Oxide Synthesis and Function
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Can NO be consider an unconventional neurotransmitter
NO acts as a retrograde messenger during LTP in the hippocampus and LTD in
cerebellum and has been involved in neurotoxicity mediated by NMDA receptors
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Non-classical neurotransmitters
Nitric Oxide
PeptidesATP and Adenosine
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5/29Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Peptides are synthesized in the cell body and released from large dense core vesicle
Peptides co-localize with other
neurotransmitters
Peptides are transported
in vesicles along withprocessing enzymes
as pro-peptides by fast
axonal transport
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Nolte J, Integrated Neuroscienc
Peptides use different types of synaptic vesicles and release mechanis
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FIGURE 20-4: Neuropeptides and conventional neurotransmitters are released from different parts of the nerve terminal
neuromuscular junction containing both large dense-core vesicles (containing the neuropeptide SCP) and small synaptic vesicle
(containing acetylcholine) was stimulated for 30 min at 12 Hz (3.5 s every 7 s). Depletion of the small clear vesicles at the muscleface and of the peptide granules at the nonmuscle face of the nerve terminal was observed. After stimulation, there was an incre
in the number of large dense-core vesicles within one vesicle diameter of the membrane. (Adapted from Karhunen et al., 2001.)
Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Biosynthesis of Peptides
Multiple peptides can be derived from the same gene. Peptides are synthesized as lo
precursor molecules and then cleaved by specific proteases
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
FIGURE 20-10: Serpentine (seven-transmembrane-domain) receptors for peptides have binding for their peptide ligands
within the membrane and in the NH2-terminal loop.
G-protein
Neuropeptide Receptors
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
Function of Neuropeptides: NPY
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Role of leptin and hypothalamic peptides in the control of appetit
WT vs. ob/ob
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Complex control of appetite involves several hypothalamic peptid
Adapted from Flier, Cell, 116, 342
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Non-classical neurotransmitter
Nitric Oxide
PeptidesATP and Adenosine(purinergic neurotransmitters)
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Purinergic neurotransmitters: Adenosine and ATP
ATP, ApnA
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Copyright 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.
Purine release and metabolism
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Nucleotide degradation and salvage pathway
Lesch-Nyhan syndrome
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The structure of the different nucleoside transporters is not known but
they transport nucleoside analogs that act as therapeutic drugs for the
treatment of cancer or AIDS (AZT).
Adenosine produces vasodilation and dipyridamole, an inhibitor of
adenosine transporter, increases its levels extracellularly and thus, isused clinically to produce coronary vasodilation
ENTs CNTs
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A1 agonist binding (3H-CPX)
A1 is coupled to Gi/o and activation has been
implicated in the anxiolytic, anticonvulsant,
analgesic and sedative actions of adenosine.
Adenosine A1 receptor agonists have being
proposed as neuroprotective agents in the
treatment of stroke because binding of adenosto presynaptic A1 receptors inhibits glutamate
release while activation of postsynaptic A1
receptors opens K+ and Cl- channels and
hyperpolarizes the cell. Also, A1R activation
inhibits microglia activation.
A t f ti
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A2A immunostaining
A2A is highly expressed in dorsal
striatum, nucleus accumbens and
olfactory tubercle.
In the straitum, A2A , which is couto Gs inhibits D2R action.
D2R is coupled to Gi, therefore A
antagonists are being tested as
potential drugs for the treatment
Parkinsons disease.
Methylxanthines such as caffeineas antagonists of A2A receptors
A2A receptor function
A2B receptors are present in endothelial cells, where they regulate vascular
permeability. Both A2A and A2B receptors contribute to vasodilation.
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Different role of purinergic receptors in synaptic plasticity
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