3 - Neurotransmitters Flashcards
Classification of Neurotransmitters
Selected Neuropeptide Transmitters
List the neurotransmitters in the classifical classification
Acetylcholine
List the neurotransmitters that are monoamines
Epinephrine
Norepinephrine
Dopamine
Serotonin
Histamine
list the neurotransmitters that are amino acids
GABA (πΎ-aminobutyric acid)
Glycine
Glutamate and Aspartate
List the neurotransmitters that are soluble gases
nitric oxide (NO)
carbon monoxide (CO)
list neurotransmitters that are lipids (endocannabinoids)
Anandamide
List the large molecule neuropeptide families
hypothalamic peptides
pituitary peptide hormones
brain-gut peptides
brain-endocrine peptides
brain-skin peptides
Trophic factors
Neuropeptide Transmitters - list the hypothalamic releasing hormones
thyrotropin releasing hormone
luteinizing hormone releasing
somatostatin
Neuropeptide Transmitters - list the pituitary peptides
adrenocorticotropic hormone
Ξ²-endorphin
βΊ-melanocyte stimulating hormone
prolactin
luteinizing hormone
growth hormone
oxytocin
vasopressin
thyrotropin
Neuropeptide Transmitters - List the Gut-Brain Peptides
Leu-, Met-Enkephalin
Substance P
Gastrin
Cholecystakinin
Vasoactive intestinal polypeptide
Insulin
Glucagon
Neurotensin
Neuropeptide Transmitters - list the Growth Factors
Nerve growth factor
Brain-derived neurotropic factor
Neuropeptide Transmitters - others
bradykinin
Angiotensin II
Calcitonin
Steps in Neurochemical Transmission (know this down cold)
Acetylcholine
- First neurotransmitter discovered
- Released by all preganglionic neurons of autonomic nervous system and postganglionic parasympathetic neurons
- Released at neuromuscular junction
- Many brain pathways
- Many pharmacological agents interact with acetylcholine receptors
- Role in cognitive function
Acetylcholine synthesis
- Precursors
-Acetyl-CoA from Kreb cycle activity
-Choline from the diet β lecithin is a good dietary source of choline - Primary synthetic Enzyme
-choline acetyltransferase - Rate-limiting step of synthesis is Choline uptake into the presynaptic terminal
Presynaptic Cholinergic Neuron
functions in storage and release of neurotransmitters
* Storage
-Vesicular acetylcholine transporter (VAT)
-active transport
-counter ions (ATP)
* Release
-Involves vesicle docking and fusion with cell membrane
-calcium dependent
-Botulinum toxin sensitiveβspecific presynaptic ganglioside
Acetylcholine inactivation
-
Acetylcholinesterase (AChE)
β Bound to post-synaptic membrane
β Mediates hydrolysis of acetylcholine to choline and acetate
β High catalytic activity
β Primary target of nerve gas agents and organophosphate pesticides (they inhibit AChE)
Acetylcholine Receptors
-
Nicotinic
β Ligand-gated cation channels
β Heterologous pentamers
β Subunit families: βΊ1-βΊ10, Ξ²2-Ξ²5, Delta, Epsilon, Gamma
β Neuromuscular junction
β Subtype N1 (Nm)
β Autonomic ganglia, adrenal medulla and brain
β N2 (N_N) subtype -
Muscarinic
β G-protein-linked
β Single subunit or dimer of two subunits
β Subtypes: M1-M5
β Peripheral end-organs innervated by the parasympathetic nervous system
β Wide distribution in the brain
Central Cholinergic Pathways
-
Basal forebrain to cortex and cingulate gyrus
β Cognition, attention
β Dementia therapy -
Septo-hippocampal
β Memory
β Dementia therapy -
Brainstem projections
β Autonomic functions -
Striatal interneurons
β Motor system
β Extrapyramidal
β Parkinsonβs therapy
GABA (Gamma - Aminobutyric Acid)
- The primary inhibitory transmitter in the nervous system
- Inhibitory electrophysiological effects are produced by increasing membrane chloride influx through GABA-A receptors
- Along with glutamate (which is excitatory), it regulates the overall tone of nervous system activity
- It is implicated in etiology of many brain diseases including Huntington disease, epilepsy, alcoholism, depression
- Mediates the effects of most central nervous system depressant drugs
GABA Synthesis
- Kreb cycle shunt pathway
- Precursor
β Glutamate -
Rate-limiting enzyme
β Glutamic acid decarboxylase (GAD) - GAD isoforms
β GAD65, GAD67 - Enzyme co-factor
β Pyridoxal phosphate (vitamin B6)
β B6 deficiency may present with seizures
GABA Storage and Release
-
Storage
β Active transport into synaptic vesicles
β Vesicular GABA transporter (VGAT) -
Release
β Vesicular, calcium-dependent
β Non-vesicular, calcium-independent
β Involves reversal of presynaptic uptake protein function
GABA Inactivation
-
Reuptake by presynaptic neuronal transporters
β Re-packaged in synaptic vesicles -
Reuptake by glial transporters
β Enzymatic degradation
β Several key metabolic enzymes involved
GABA Metabolism
-
Enzymatic degradation
β GABA Transaminase (GABA-T) - Converts GABA to succinic semi-aldehyde (SSA)
- SSA converted to succinate by SSA dehydrogenase
GABA Receptors
-
GABA-A
β Ligand-gated chloride channel
β Heterologous pentamer
β Subunit families - a1-6, b1-4, g1-4, d1-2, t1, e1, r1-3
β Mediates βfastβ inhibitory transmission (millisecond time course) -
GABA-B
β G-protein-linked
β Heterologous dimer - GABR1, GABR2
β Mediates βslowβ inhibitory
transmission
β Variably long time course
GABA-A Receptor Function
- GABA-A activation causes neuronal inhibition
β Depresses activity of the CNS - Agonists are used for
β Insomnia
β Anxiety
β Epilepsy
β General anesthesia
Major GABA Pathways
-
Projection pathways
β Hippocampus
β Basket cells, stellate cells
β Cerebellum
β Purkinje cells, Golgi cells
β Striatonigral, pallidonigral
β Neurons in striatum and globus pallidus project to substantia nigra (Huntington disease)
β Thalamocortical
β Thalamic nuclei project to
neocortex (Absence epilepsy) -
Interneurons
β Ubiquitous including neocortex, basal ganglia, cerebellum, spinal cord
Glutamate
- The primary excitatory transmitter in the nervous system
- Excitatory electrophysiological effects via increased cation conductance through activated glutamate receptors
- Along with GABA (which is inhibitory), it regulates the overall tone of nervous system activity
- Glutamate and related excitatory amino acids (EAAs) implicated in etiology of many neurological and psychiatric diseases including schizophrenia, epilepsy, stroke and neurodegenerative illnesses
- Small but growing number of clinically relevant pharmacologic agents target glutamatergic neurons
Glutamate Synthesis
- Aminotransferase
β Expressed in all cells - Krebs cycle enzyme
β Uses vitamin B6 as co-factor - Glutamine synthetase
β Expressed only in glia
β Uses ATP as a co-factor - Glutaminase
β Expressed only in neurons
Glutamate Neurochemistry
Glutamate Receptors
Glutamate Receptor Function
Major Glutamate Pathways
Brain Monoamines
Catecholamine Synthesis
Catecholamine Neurochemistry
Dopamine Receptors
Major Dopamine Pathways
Major Dopamine Functions
Norepinephrine Receptors
Major Norepinephrine Pathways
Major Norepinephrine Functions
Serotonin Neurochemistry
Serotonin Receptors
Major Serotonin Pathways
Major Serotonin Functions
Endogenous Opioid Neuropeptides
Major Opioid Receptors
Neurotransmitter Colocalization
Neurotransmitter Colocalization
Neurotransmitters summary