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

 Perfuse heart B
 Heart B slows
 chemical = vagusstoff ~
A
-
B

 Repeat w/ accelerator nerve

HR increases

Acceleransstoff ~
A
+
B

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 acetyltransferase choline + acetyl CoA ACh

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: D
1
, D
2
, etc. ~

Norepinephrine

Loewi’s acceleranstoff
 Peripheral N.S.

Sympathetic neuroeffector junction

Adrenal glands
 Central N.S.

Hypothalamus

Locus coeruleus
 Alpha & Beta receptor subtypes

NE a
& NE b
~

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

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
 g
-aminobutyric acid
 Major NT in brain inhibitory system
 Receptor subtypes

GABA
A
- controls Cl- channel

GABA
B
- 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 ~

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