Neurotransmitter Systems Lecture (Dr. Karius) Flashcards
What is produced almost exclusively in the MIDLINE RAPHE NUCLEI?
- Serotonin
An autoimmune response that destroys the neurons of the TUBEROMAMMILLARY NUCLEUS is most likely to directly DECREASE release of which Neurotransmitter?
- Histamine
What is the Correct order of Synthesis of the Monamines derived from Tyrosine?
1) Dopamine
2) Norepinephrine
3) Epinephrine
Neurons which release which Neurotransmitter as their Primary Transmitter are also likely to release measurable quantities of DOPAMINE and NOREPINEPHRINE?
- EPHINEPHRINE
Dopamine
CENTRAL LOCATION:
- Basal Ganglia
- VTA
FUNCTIONS:
- Motor Control
- Pleasures
- Consciousness
IONOTROPIC RECEPTORS:
- None
METABOTROPIC RECEPTORS:
- D1, D2, D3
OTHER
- TYROSINE Derivative
Norepinephrine
CENTRAL LOCATION:
- Pons/ Brainstem
FUNCTIONS:
- Wakefulness
IONOTROPIC RECEPTORS:
- None
METABOTROPIC RECEPTORS:
- ALPHA and BETA Adrenergics
OTHER
- TYROSINE Derivative
Epinephrine
CENTRAL LOCATION:
- Brianstem
FUNCTIONS:
- Wakefulness
IONOTROPIC RECEPTORS:
- None
METABOTROPIC RECEPTORS:
- ALPHA and BETA Adrenergics
OTHER
- TYROSINE Derivative
Serotonin
CENTRAL LOCATION:
- Brainstem (RAPHE NUCLEUS)
FUNCTIONS:
- Mood, Wakefulness
IONOTROPIC RECEPTORS:
- 5HT3 (VOMITING)
METABOTROPIC RECEPTORS:
- Multiple: 5HT6 (MOOD)
OTHER
- TRYPTOPHAN Derivative
Histamine
CENTRAL LOCATION:
- Hypothalamus
FUNCTIONS:
- Waking
IONOTROPIC RECEPTORS:
- None
METABOTROPIC RECEPTORS:
- H1 and H2
OTHER
- HISTIDINE Derivative
Acetylcholine: Central Location
- Midbrain
- Pond
- The Striatum
Acetylcholine: General Functions
- Crucial in producing Consciousness, but not awareness (Brain AROUSAL Mechanisms)
- Control of VOLUNTARY MOTION
- Initiation of REM Sleep
Acetylcholine: Vesicular Storage
- ACh sotred in CLEAR VESICLES
- Moved into Vesicles by the Vesicular ACh Transporter Protein (VAChT)
Acetylcholine: Catabolism
- ACETYLCHOLINESTERASE (Aka true or specific Cholinesterase) is bound to the Post-Synaptic Cell Membrane
Acetylcholine Receptors
MUSCARINIC
MUSCARINIC RECEPTORS:
- Four or Five different types, all activated by MUSCARINE
- SERPENTINE Receptors
- G Protein Coupled
Receptors:
1) M1 (Neuronal): INCR IP3/ DAG (Gq) —> INCR Ca2++
2) M2 (Cardiac): DECR cAMP (Gi) —> INCR K+ Efflux
3) M3 (Smooth Muscle of Bronchi, Vasculature; Endothelial Cells of Vasculature (NO)): INCR IP3/ DAG (Gq) —> INCR Ca++
4) M4 (Glands): DECR cAMP
5) MARKGENDI5: INCR IP3/ DAG
Acetylcholine Receptors
NICOTONIC
Nicotinic Receptors:
- Located at:
a) NMJ
b) Autonomic Ganglia
c) Other parts of the CNS
5 Subunits: (16 Genes)
- Alpha (1 - 9 Genes)
- Beta (2 - 5 Genes)
- Gamma (1 Gene)
- Delta (1 Gene)
- Epsilon (1 Gene)
**CHANGING the SUBTYPES changes the way the Channel Behaves!!!!!!
Nicotinic Receptor Description
- Nicotinic Receptors are INOTROPIC and allow for SODIUM ENTRANCE, although some Neuronal forms allow for Significant Ca++ INFLUX!!!!!
Excitatory Amino Acids
- Glutamate
- Aspartate
- Taurine
Inhibitory Amino Acids
- GABA (Gamma- Amino Butyric Acid)
- Glycine
Location of GABA
- Cerebellum
- Cortex
- Retina
Functional Roles of GABA
- MAJOR INHIBITORY Neurotransmitter in the HIGHER CNS
- Critical for producing Consciousness/ Awareness (BRAIN AROUSAL MECHANISMS)
- Control fo VOLUNTARY MOTION
How is GABA Made?
- Glutamate DECARBOXYLASE (GAD)
- Derived from GLUTAMATE
How is GABAs action Limited?
- REUPTAKE
- Catabolism by GABA-TRANSAMINASE
GABA Receptors
1) GABA a
2) GABA b
GABA a Receptor
- Inotropic
- 5 Subunits
- CHLORIDE CONDUCTANCE
- BENZODIASEPINE Site POTENTIATES!!!!!!!!!
GABA b Receptor
- Serpentine
- HETERODIMER G protien (Gi and Gq)
- DECR Adenylyl Cyclase —–> INCR K+ Efflux
- DECR IP3/ DAG —-> DECR Ca++ Influx
- End Result: HYPERPOLARIZATION!!!!!!!!!!!!!!!
GABA Receptors and General Anesthetics
- A large number of GABA Receptors (Mostly GABA a) have been fousn at Extra-Synaptic locations throughout the Cortex. They appear to be activated by “Free Floating” GABA
- Many General Anesthetics are now postulated to produce Anesthesia by activating THESE RECEPTORS
Locations of Glycine
- SPINAL CORD!!!!!!!
- Brianstem
- Forebrain (Less than GABA)
General Functions of Glycine
- Mediates many Spinal Inhibitions (Reflexes and their Modification)
Glycine Receptors
- Inotropic
- PENTAMER
- Alpha Subunit: GLYCINE BINDING
- Beta Subunit is STRUCTURAL
- CHLORIDE CHANNEL
- Blocked by STRYCHNINE!!!!!!!!!
Opioid Peptides
** These Neurotransmitters are peptides coded for by Genes
- Tachykinins (Includes Substance P)
- OPIOIDS!!!!!!
- ENDOCANNABINOIDS!!!!!!!
- Somatostatin
- CCK
- CGRP
Neurotransmitters Released from Opioids
1) ENDORPHINS (Endogenous Morphines)
2) ENKEPHALINS
3) DYNORPHINS
4) Nociceptin
Opioid Locations
- Basal Ganglia
- Hypothalamus
- Parabrachial Nuclei and Raphe Nuclei
General Functions of Opioids
- Modification of NOCICEPTIVE INPUTS (Neurophysiology of PAIN)
- Modification of Mood/ Affect (LIMBIC SYSTEM)
Opioids are based on 4 Precursor Molecules
1) PROENKEPHALIN (Tyr- Gly - Gly - Phe - X)
a) Met- Enkephalin
b) Leu - Enkephalin
2) PRO- OPIOMELANOCORTININ (POMC)
- Beta Endorphins
3) PRODYNORPHIN
- 3 Molecules of Leu-Enkephalin
- Dynorphins (1-8 and 1-17)
4) ORPHANIN FQ (Aka Nociceptin)
How are Opioids made?
- Since peptide, coded and created via DNA/ RNA/ Protein Synthetic Machinery
How to we limit the action of Opioids?
- ** ENZYMATIC, possible after REUPTAKE
- Enkephalinase A and B
- Aminopeptidase
Opioid Receptors
1) Mu Receptors
2) Kappa Receptors
3) Delta Receptors
Mu Receptors
- Serpentine Receptor
- ANALGESIA (Pain)
- RESPIRATORY DEPRESSION
- EUPHORIA
- Sedation
- Constipation
Kappa Receptors
- Serpentine Receptor
- ANALGESIA (Pain)
- Diuresis
- Miosis (Eye Drooping)
- DYSPHORIA
Delta Receptors
- Serpentine Receptor
- ANALGESIA
Opioid Receptor Conclusion
- They are all SERPENTINE Receptors and INHIBIT ADENYLYL CYCLASE
Indirect Ion Effects:
1) Mu: INCR K+ Efflux and Hyperpolarize
2) Kappa and Delta: DECR Calcium
Endocannabinoids
1) ANANDAMIDE:
- “Bliss”
- Arachidonic Acid + Ethanolamine
2) 2- ARACHIDONYLGLYCEROL
- Arachidonic Acid esterified into he middle (#2) position of Glycerol
Endocannabinoid Locations
1) Hippocampus: MEMORY Formation
2) BASAL GANGLIA: AFFECT MOTOR!!!!!!!!!!
3) SPINAL CORD: MODULATION of NOCICEPTION!!!!!!!!!!!!!
4) Neocortex: Neuroprotective?
Endocannabinoid Receptors
1) CB-1
2) CB-2
CB-1 Receptor
- Axons and PRESYNAPTIC Terminals of EAA and GABA Synapses
- Gi Protein-Coupled Receptor
- Reduced Neurotransmitter Release
- Binds to either ANADAMINE or 2-AG well!!!!!!
CB-2 Receptor
- Found in BRIAN (Microglia, NOT Neuron)
- IMMUNE SYTEM and GUT
- ANTI INFLAMMATORY
- IN Brain, cause MACROPHAGES to remove BETA-AMYLOID!!!!!!
Acetylcholine
CENTRAL LOCATION:
- Pons/ Midbrain
FUNCTIONS:
- Wakefulness
IONOTROPIC RECEPTORS:
- Nicotinic (Sodium)
METABOTRPIC RECEPTORS:
- Muscarinic
OTHER:
- Separate from ANS
GABA
CENTRAL LOCATION:
- HIGHER CNS
FUNCTIONS:
- Motor Control
- Consciousness
IONOTROPIC RECEPTORS:
- GABA-A (Chloride)
METABOTRPIC RECEPTORS:
- GABA-B
OTHER:
- Extra Synaptic Receptors (Anesthetics)
Glycine
CENTRAL LOCATION:
- Spinal Cord
FUNCTIONS:
- Almost ALL INHIBITION
IONOTROPIC RECEPTORS:
- Glycine (Chloride)
METABOTRPIC RECEPTORS:
- None to Date
OTHER:
- None
Opioids
CENTRAL LOCATION:
- Hypothalamus/ Medulla
FUNCTIONS:
- Modulation of PAIN/ Production of PLEASURE
IONOTROPIC RECEPTORS:
- None
METABOTRPIC RECEPTORS:
- Mu. Kappa, Delta
OTHER:
- Endorphins
- Dynorphin
- Enkephalins
- Nocicpetin
Endocannabinoids
CENTRAL LOCATION:
- Multiple/ Wide Spread
FUNCTIONS:
- Modulation of Pain/ Neuroprotection
IONOTROPIC RECEPTORS:
- None
METABOTRPIC RECEPTORS:
- CB1
- CB2
OTHER:
- Anandamide and 2-AG
