Neurotransmitters & Recptors Flashcards
1
Q
Distribution of Cholinergic neurons
A
- cholinergic neurons in vertebrate NS
- motor neurons
- Autonomic NS
- Preganglionic sympathetic and parasympathetic
- postganglionic parasympathetic
- neurons regulating arousal and sleep in brainstem and forebrain
- local interneurons in other brain regions
- project locally within the region
2
Q
Synthesis, release, removal of acetylcholine
A
- synthesized from precursors in Acetyl-CoA and choline in presynaptic terminal
- loaded into SVs by vesicular transporter
- degraded in cleft by acetylcholinesterases (leaves choline which is taken up
- acetate diffuses away
3
Q
Nicotine acetylcholine receptors
A
- ionotropic receptors permeable to cations
- fast EPSPs
- structure: 5 subunits + several genes for diversity
- distribution:
- at NMJ
- pre and post ganglionic parasympathetic
- preganglionic sympathetic
- many cholinergic synapses in brain
- nicotine, a-bungarotoxin, curare act on nicotine receptors
4
Q
Muscarinic acetylcholine receptors
A
- metabotropic receptors
- activation leads to decrease or increase in K+ conductance
- slower EPSPs/IPSPs
- distribution:
- targets of parasympathetic innervation (heart, smooth muscle)
- forebrain regions (striatum)
- blockers: atropine (pupillary dilation), scopolamine (prevents motion sickness), ipreatopium (asthma treatment)
5
Q
Myasthenia Gravis
A
- disease that interferes with neurotransmission at NMJ
- faster fatigue during repetitive stimulation
- mEPPs smaller
- cause: autoimmune disease
- antibodies against nAChRs generated
- treatment: acetylcholine esterase inhibitors
- less degradation of acetylcholine
6
Q
Distribution of Glutamate
A
- NT of most excitatory synapses throughout CNS
- more than 50% of all synapses in the brain
- NT of many primary sensory cells (photoreceptors, olfactory receptors)
7
Q
Synthesis, release and removal of glutamate
A
- synthesized from glutamine in presynaptic terminal
- loaded into SVs by vesicular transporter
- released glutamate taken up into glia and neurons by excitatory aa transporters
- glutamine taken up by glia is converted to glutamine and shuttled back to neurons
8
Q
Ionotropic glutamate receptors
A
- AMPA, NMDA, Kainate
- all cation permeable
- all have 4 subunits and multiple genes
- distribution:
- most glutamatergic synapses in brain have AMPA and NMDA
- Kainate receptors present at some synapses
9
Q
NMDA receptors
A
- permeable to cations; calcium activates postsynaptic signalling pathways
- at negative membrane potentials, channel pore blocked by Mg2+
- opens only in response to glutamate release and post synaptic depolarization
- COINCIDENCE DETECTOR
- glycine or D-serine as coagonist
10
Q
Metabotropic glutamate receptors
A
- 3 groups
- post- and presynaptic localization
- postsynaptic: trigger second messenger cascades modulating excitability
- presynaptic: diminish NT release (inhibitory)
11
Q
GABA and glycine distribution
A
- GABA is an amino acid NT
- most abundant inhibitory NT in brain (30% of synapses)
- glycine mainly at inhibitory synapses in spinal chord
12
Q
GABA synthesis, release, removal
A
- synthesized from glutamate in presynaptic terminal
- SV loading by vesicular inhibitory AA transporter
- released GABA taken up into glia and neurons by GABA transporters
13
Q
Glycine synthesis, release, removal
A
- synthesized from serine in presynaptic terminal
- SV loading by vesicular inhibitory aa transporter
- released glycine taking up into glia and neurons by glycine transporter
14
Q
Ionotropic GABA and glycine receptors
A
- GABA(A)
- permeable to Cl- (usually IPSP)
- structure: 5 subunits, several genes
- benzodiazepines and barbiturates: positive modulators; used as sedatives, anxiolytics, and anticonvulsants
- bind to channel and allow them to be open longer… more Cl- influx repolarizing membrane
Glycine receptors: permeable to Cl-
-inhibited by strychnine (causes convulsions… uncontrolled excitation)
15
Q
Metabotropic GABA receptors
A
- GABA(B)
- Activation of G proteins leads to increase K+ conductance
- slow IPSPs
- presynaptic GABAB receptors diminish NT release
16
Q
Distribution and function of dopamine
A
- substantia nigra and ventral tegmental area
- project to cortex and striatum
- functions:
- facilitation of body movement (Parkinson’s)
- motivation and reinforcement (addiction)
- regulate cognitive functions (psychiatric disorders)
17
Q
Synthesis and removal of dopamine
A
- synthesized from tyrosine
- released DA taken up into glia and neurons by domaine transporters
- DAT inhibited by cocaine, so in synapse longer
- DA degraded in neurons by monoamine oxidase
- MAO inhibitors used as antidepressants (prevents breakdown)
18
Q
Dopamine receptors
A
- only metabotropic
- receptor activation can lead to increase or reduced post synaptic excitability (depending on which G protein)
- DA antagonists used to treat schizophrenia
- L-DOPA (precursor of DA) used to treat Parkinson’s symptoms
19
Q
Distribution and function of norepinephrine
A
- sympathetic ganglia
- fight or flight
- locus coeruleus in brain stem
- influences sleep and wake
20
Q
Distribution and function of epinephrine
A
- in rostral medulla
- involved in autonomic functions
- adrenal glands produce 80% of epinephrine (20% of norepinephrine)
21
Q
Norepinephrine and Epinephrine synthesis and removal
A
- NE synthesized from DOPAMINE
- released NE taken up into glia and neurons by NE transporter
- NET inhibited by amphetamines
- degraded in neurons by MAO
- MAO used as antidepressants
22
Q
Adrenergic receptors
A
- metabotropic
- bind E and NE
- different classes for different G proteins
- increase or decrease excitability
- peripheral: smooth muscle contraction/relaxation
- increased heart and muscle force
- glandular secretion
- antagonists and agonists used pharmacologically
- beta blockers (decrease excitability)
23
Q
Distribution and function of serotonin
A
- in raphe nuclei
- regulate:
- sleep and wake
- arousal
- mood and emotions
24
Q
Synthesis and removal of serotonin
A
- synthesized from tryptophan
- taken up into glia and neurons by serotonin transported
- SERT inhibitors used as antidepressants
- degraded by MOA
25
Serotonin receptors
- also called 5-HT receptors
- metabotropic receptors with different classes
- increase/decrease excitability
- also 1 group of ionotropic receptors
- non-selective, mediate fast EPSPs
26
Histamine distribution and function
- in hypothalamus
- regulate sleep and wake
- antihistamines have sedative effect
27
Histamine synthesis and removal
- synthesized from histidine
- taken up into glia and neurons
- degraded by MAO
28
Histamine receptors
- metabotropic
| - increase or decrease excitability
29
Purines distribution and function
- Purine NTs: ATP and adenosine
- ATP in all SVs
- coreleased with other NTs
- adenosine generated through breakdown of ATP in extracellular space
- functions:
- neuron - glia communication
- nociception
- respiratory response to hypoxia
30
Purinergic receptors
- 3 classes: P1, P2Y, P2X
- P2X only ionotropic receptor
- all classes expressed throughout NS and in neuronal tissue
- caffeine blocks P1: responsible for stimulant effect
31
Classification of peptide NTs
- more than 100 peptide NTs
- many are also hormones
- released from neurons in CNS and non-neuronal cells in periphery
- ex:
- brain-gut peptides
- opioid peptides
- pituitary peptides
- hypothalamic peptides
32
Synthesis of peptide NT
- synthesized in ER as pre-propeptides
- after cleavage of signal sequence, propeptides packaged into dense core vesicles
- proteolytic cleavage of propeptides in vesicles
- released neuropeptides degraded by peptidases on extracellular surface of PM
33
Release of peptide NT
- neurons often co release peptides and small molecules NTs
- stored in different vesicles
-released perisynaptically following high frequency stimulation
34
Receptors for peptide NTs
- mostly metabotropic
- high affinity for peptide because post synaptic targets can be far away due to paracrine transmission
- opioid receptors:
- agonists are plank alkaloid: morphine; synthetic opioids: methadone and fentanyl
- antagonist: naloxone
35
Synthesis of endocannabinoids
- unsaturated fatty acids produced by enzymatic leakage of lipids
- synthesis regulated:
- Ca2+ rise in postsynaptic neuron leads to endocannabinoids generation
- due to structure they can diffuse across PM and bind to metabotropic receptors on presynaptic neurons
- neuromodulator
- not packaged in SV
- exist in cytoplasm
36
Mechanism of endocannabinoids
- diffuse across PM when Ca2+ rise in postsynaptic neuron
- bind to presynaptic metabotropic receptors
- reduce NT release at GABAergic synapses
37
THC
- agonist of CB receptors
| - CB1 receptor highly expressed in basal ganglia: depression of activity in these areas = altered cognitive state
