Neurotransmitters Lesson 13

Neurotransmitters n Chemical messengers l Signal between cells n Released at axon terminal l By action potentials n Metabolism by enzymes l Synthesis (anabolism) l Degradation (catabolism) ~

Chemical Signaling n Otto Loewi had a dream l Chemical Signal? l How can it be demonstrated? n Frog Heart Preparation ~

n Stimulate Vagus l Heart rate slows ~ electrical stimulation -

n Stimulate A l Collect fluid ~ A B -

A B n Perfuse heart B n Heart B slows l chemical = vagusstoff ~ -

B n Repeat w/ accelerator nerve l HR increases l Acceleransstoff ~ A +

The Chase Is On n Search for chemical neurotransmitters (NT) n Criteria l Found in axon terminals l Released by action potentials l Synthesis identified l External application mimic normal response l Externally applied same mechanism as NT ~

Acetylcholine - ACh n Loewi’s vagusstoff n Peripheral N.S. l Skeletal muscle contraction n Autonomic NS l Ganglia l Parasympathetic neuroeffector junction n Central N.S. - widespread l Hippocampus l Hypothalamus ~

Acetylcholine - ACh n Receptor subtypes l Nicotinic (nACh-R) u ionotropic l Muscarinic (mACh-R) u metabotropic n Degraded by acetylcholinesterase l AChE l Enzyme found in synapse ~

ACh Synthesis choline+ acetyl CoAACh choline acetyltransferase

Monoamines n 2 groups l Amino acid precursors l Catecholamines - tyrosine l Indolamine - tryptophan n All degrade by monoamine oxidase (MAO) n Affected by many of same enzymes & drugs ~

Monoamines n Catecholamines l Dopamine - DA u Dopaminergic l Norepinephrine - NE u Noradrenergic l Epinephrine - E u Adrenergic ~ n Indolamines l Serotonin - 5HT u Serotonergic

Dopamine n Only in central nervous system l mostly inhibitory systems n Reward n Schizophrenia n Movement l Nigrostriatal Pathway n At least 5 DA-R types: D 1, D 2, etc. ~

Norepinephrine n Loewi’s acceleranstoff n Peripheral N.S. l Sympathetic neuroeffector junction l Adrenal glands n Central N.S. l Hypothalamus l Locus coeruleus n Alpha & Beta receptor subtypes NE  & NE  ~

Serotonin n NOT a catecholamine n Peripheral l 98% in blood & smooth muscle n Central N.S. l Raphe nucleus l Hypothalamus n R subtypes: 5HT 1 & 5HT 2 ~

Amino Acid Neurotransmitters n Unmodified amino acids l Nonessential amino acids n Glutamate l Primary NT in CNS excitatory neurons l Metabotropic (mGlu-R) l Iononotropic: NMDA-R; AMPA-R n Excitotoxicity l Following brain injury l Elevated Glu activity

Amino Acid Neurotransmitters n GABA – GABAergic  -aminobutyric acid n Major NT in brain inhibitory system n Receptor subtypes l GABA A - controls Cl- channel l GABA B - controls K+ channel ~

Neuropeptides n Chains of amino acids l Synthesis in soma l Axonal transport n Often neuromodulators l alters sensitivity of neurons l slower, longer-lasting effects n Substance P - pain signaling ~

Neuropeptides: Endorphins n Endogenous + morphine = Endorphin l Also opioids l Opiate drugs are ligands l analgesia, euphoria ~

Some Other NTs n Histamine l Inflammatory Response n Nitric Oxide - It’s a gas l Retrograde messenger l Not stored in vesicles n Endocannabinoids l Anandamide, 2 - AG n Purines l ATP, GTP ~

Focus on n ACh n NE n DA n 5HT n GABA n Endorphins