Neurotransmitters

Lesson 13

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 ~

Stimulate Vagus Heart rate slows ~

electrical stimulation

-

Stimulate A Collect fluid ~

A B-

A B

Perfuse heart B Heart B slows

chemical = vagusstoff ~

-

B

Repeat w/ accelerator nerve HR increases Acceleransstoff ~

A+

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 ~

ACh Synthesis

choline + acetyl CoA ACh

choline acetyltransferase

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 ~

Focus on

ACh NE DA 5HT GABA Endorphins