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Non-Classical Neurotransmission

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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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