Transcript NEUROTRANSMITTERS - University of Kansas Medical Center

NEUROTRANSMITTERS
Classic Characteristics:
Synthesized in the neuron.
 Become localized in presynaptic terminal.
 Bind to receptor site on postsynaptic
membrane.
 Removed by a specific mechanism from
its specific site of action.

Classification

Small molecule transmitters:
Amino acids:
Dietary amino acids.
GABA
Monoamines:
Catecholamines.
Indoleamines.

Acetylcholine.
Amino Acids

Dietary:
Aspartate.
Glycine.

Gamma aminobutyric acid (GABA):
From decarboxylation of glutamate.
Monoamines

Catecholamines:
Derived from tyrosine.
Include:
Dopamine.
Norepinephrine.
Epinephrine.
Monoamines

Indoleamine:
Derived from tryptophan.
Includes:
Serotonin.
Glutamate
Most common excitatory neurotransmitter
in the CNS.
 Synthesized in mitochondria.
 Inactivated by reuptake:

Via nerve terminals.
Via astrocytes:
Convert glutamate back to glutamine.
May resupply nerve terminal.
Glutamate

Found in:
Cerebral cortex.
Striatum.
Dentate gyrus (hippocampus).
Cerebellum.
Spinal cord.

Excitatory influences on basal nuclei.
Aspartate
Found throughout brain and spinal cord.
 Effects are usually excitatory.

Glycine

Common inhibitory neurotransmitter.
Increases chloride conductance in
postsynaptic membrane.
Blocked by strychnine.
Converted from serine.
 Inactivated by reuptake.

Glycine

Found in:
Interneurons of spinal cord:
Renshaw cells.
Neurons of subthalamic nuclei projecting to
globus pallidus.
GABA
Gamma aminobutyric acid:
 Most common inhibitory neurotransmitter
in CNS.

Increases chloride conductance.

Inactivated via reuptake:
Into nerve terminals.
Into glial cells.
GABA
Site of action of anxiolytic drugs such as
Valium and Librium.
 Inhibited by penicillin:

Causes over-excitation and seizure activity in
brain.
GABA

Found in:
Granule cells of olfactory bulbs.
Amacrine cells of retina.
Purkinje cells and basket cells of cerebellum.
Hippocampus.
Basal ganglia.
Numerous interneurons.
GABA
GABAergic neurons of caudate nucleus
and putamen project to substantia nigra
and globus pallidus.
 Reduced concentrations in patients with
Huntington’s chorea:

May contribute to presence of uncontrolled
involuntary movements.
Dopamine
Usually inhibitory.
 Present in neurons of substantia nigra:

Nigrostriatal dopaminergic pathway projects
to putamen and caudate nucleus.
Loss of inhibitory influences may be
associated with Parkinson’s disease.
Dopamine

Other pathways project to limbic system
components:
Malfunctioning may be associated with
schizophrenia.
Dopamine

Also found in:
Neurons from hypothalamus to hypophysis.
Retina:
Role in lateral inhibition (focusing effect).
Olfactory bulb.
Norepinphrine
Usually inhibitory.
 May be released into neuropile from axon
varicosities filled with vesicles.

90 percent do not form synapses.
Accounts for slow-acting and long-lasting
effects following release.
May enhance neuropile neuronal activity via
lateral inhibition.
Norepinphrine

Inactivation:
Reuptake into synaptic terminal.
Uptake by effector cells (with MAO and
COMT).
Diffusion away from site.
Norepinphrine

Inactivation:
Destruction:
MAO:
Monoamine oxidase.
Intracellular.
COMT:
Catechol-O-methyltransferase.
Extracelluar.
Norepinphrine

Found in:
Locus ceruleus and Lateral tegmental nuclei.
Neurons to:
Midbrain tectum.
Thalamus, hypothalamus
Cerebral cortex, Cerebellar cortex
Medulla and spinal cord
Most postsynaptic sympathetic
neurons.
Norepinphrine Functions
Modulator– sets brain tone.
 Suppresses irrelevant stimuli.
 Enhances relevant stimuli.
 Modifies behavior, arousal, degree of
alertness, ECG activity and sleep.
 Role in mood, memory.
 Hormone regulation and homeostasis.

Norepinephrine Receptors
Alpha adrenergic receptors
 Beta adrenergic receptors:

Involve G-proteins and adenyl cyclase
activation.
Epinephrine
Usually excitatory.
 Found in neurons of:

Lower brainstem tegmentum.
Locus ceruleus.
Axons projecting rostrally to hypothalamus.
Axons projecting to intermediolateral cell
column of spinal cord (preganglionic
sympathetic neurons located here.)
Serotonin
Only present in cell bodies of neurons
located primarily in the raphe and reticular
formation (limited) of brainstem.
 Inactivated by MAO.

Serotonin

Axons project to:
Diencephalon.
Striatum.
Cerebral cortex.
Ependyma of ventricles.
Cerebellum.
Spinal nucleus of CN V
Serotonin Functions (?)
Inducing sleep.
 Pain transmission.
 Certain psychotic disorders:

Depression.

Total amnesia may occur when:
Raphe neurons are destroyed.
Serotonin stores are depleted by reserpine.
Acetylcholine
Choline is made in liver, not brain.
 Synthesized by choline acetyltransferase:

Synthesized within neuron cell body.

Degraded by acetylcholinesterase:
Synthesized within neuron cell body.
Acetylcholine

Found in neurons:
Lower alpha and gamma motor neurons.
All ANS preganglionic neurons.
All parasympathetic postganglionic neurons.
Sympathetic postganglionic neurons
innervating sweat glands.
Acetylcholine

Found in brain:
Basal nucleus of Meynert:
Axons project to cerebral cortex.
Alterations in these neurons may be
associated with Alzheimer’s.
Interneurons within striatum:
Loss of these seems to be a main feature of
Huntington’s.
Associated with limbic system.
Cholinergic Receptors

Nicotinic:
Found in spinal cord and superior colliculi.
Activate mainly sodium channels (EPSP).
Found in neuromyal junctions.
Found in autonomic ganglia.
Blocked by curare.
Cholinergic Receptors

Muscarinic:
Predominant cholinergic receptors in brain.
Principal cholinergic receptor on ANS target
organs.
Coupled to G-proteins.
Blocked by atropine.
Nitric Oxide
Neuroactive Peptides

Opioid peptides:
Include:
Endorphins.
Dynorphins.
Enkephalins.
Present in pain pathways.
Present in limbic circuits.
Present in reticular formation (enkephalins).
Neuroactive Peptides

Hormones:
Vasopressin (ADH).
Oxytocin.
Neuroactive Peptides
 Somatostatin.
 Tachykinins:
Substance P:
Excitatory transmitter in CNS and
intestinal tract.
Associated with pain pathways.
High concentration in substantia nigra.
Decreased in Huntington’s
patients.
Neuroactive Peptides
Vasoactive intestinal peptide (VIP)
 Cholecystokinin octapeptide
