Neurotransmitters
Chemical messengers Signal between cells
Released at axon terminal By action potentials
Metabolism by enzymes Synthesis (anabolism) Degradation (catabolism) ~
Chemical Signaling
Otto Loewi had a dream Chemical Signal? How can it be demonstrated?
Frog Heart Preparation ~
The Chase Is On Search for chemical neurotransmitters (NT) Criteria
Found in axon terminals Released by action potentials Synthesis identified External application mimic normal
response Externally applied same mechanism as NT
~
Acetylcholine - ACh
Loewi’s vagusstoff Peripheral N.S.
Skeletal muscle contraction Autonomic NS
Ganglia Parasympathetic neuroeffector junction
Central N.S. - widespread Hippocampus Hypothalamus ~
Acetylcholine - ACh
Receptor subtypes Nicotinic (nACh-R)
ionotropic Muscarinic (mACh-R)
metabotropic Degraded by acetylcholinesterase
AChE Enzyme found in synapse ~
Monoamines
2 groups Amino acid precursors Catecholamines - tyrosine Indolamine - tryptophan
All degrade by monoamine oxidase (MAO)
Affected by many of same enzymes & drugs ~
Monoamines
Catecholamines Dopamine - DA
Dopaminergic Norepinephrine -
NE Noradrenergic
Epinephrine - E Adrenergic ~
Indolamines Serotonin - 5HT
Serotonergic
Dopamine
Only in central nervous system mostly inhibitory systems
Reward Schizophrenia Movement
Nigrostriatal Pathway At least 5 DA-R types: D1, D2, etc. ~
Norepinephrine
Loewi’s acceleranstoff Peripheral N.S.
Sympathetic neuroeffector junction Adrenal glands
Central N.S. Hypothalamus Locus coeruleus
Alpha & Beta receptor subtypes NE & NE ~
Serotonin
NOT a catecholamine Peripheral
98% in blood & smooth muscle Central N.S.
Raphe nucleus Hypothalamus
R subtypes: 5HT1 & 5HT2 ~
Amino Acid Neurotransmitters Unmodified amino acids
Nonessential amino acids Glutamate
Primary NT in CNS excitatory neurons Metabotropic (mGlu-R) Iononotropic: NMDA-R; AMPA-R
Excitotoxicity Following brain injury Elevated Glu activity
Amino Acid Neurotransmitters
GABA – GABAergic -aminobutyric acid
Major NT in brain inhibitory system Receptor subtypes
GABAA - controls Cl- channel
GABAB - controls K+ channel ~
Neuropeptides
Chains of amino acids Synthesis in soma Axonal transport
Often neuromodulators alters sensitivity of neurons slower, longer-lasting effects
Substance P - pain signaling ~
Neuropeptides: Endorphins
Endogenous + morphine = Endorphin Also opioids Opiate drugs are ligands analgesia, euphoria ~
Some Other NTs
Histamine Inflammatory Response
Nitric Oxide - It’s a gas Retrograde messenger Not stored in vesicles
Endocannabinoids Anandamide, 2 - AG
Purines ATP, GTP ~