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NESC 2570 > Neurotransmitters & Recptors > Flashcards

Neurotransmitters & Recptors Flashcards

1
Q

Distribution of Cholinergic neurons

A
  • cholinergic neurons in vertebrate NS
    • motor neurons
    • Autonomic NS
      1. Preganglionic sympathetic and parasympathetic
      2. postganglionic parasympathetic
    • neurons regulating arousal and sleep in brainstem and forebrain
    • local interneurons in other brain regions
      • project locally within the region
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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
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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
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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)
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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
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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)
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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
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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
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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
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10
Q

Metabotropic glutamate receptors

A
  • 3 groups
  • post- and presynaptic localization
  • postsynaptic: trigger second messenger cascades modulating excitability
  • presynaptic: diminish NT release (inhibitory)
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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
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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
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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
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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)

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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
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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
Q

Serotonin receptors

A
  • 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
Q

Histamine distribution and function

A
  • in hypothalamus
  • regulate sleep and wake
  • antihistamines have sedative effect
27
Q

Histamine synthesis and removal

A
  • synthesized from histidine
  • taken up into glia and neurons
  • degraded by MAO
28
Q

Histamine receptors

A
  • metabotropic

- increase or decrease excitability

29
Q

Purines distribution and function

A
  • 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
Q

Purinergic receptors

A
  • 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
Q

Classification of peptide NTs

A
  • 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
Q

Synthesis of peptide NT

A
  • 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
Q

Release of peptide NT

A
  • neurons often co release peptides and small molecules NTs
  • stored in different vesicles

-released perisynaptically following high frequency stimulation

34
Q

Receptors for peptide NTs

A
  • 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
Q

Synthesis of endocannabinoids

A
  • 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
Q

Mechanism of endocannabinoids

A
  • diffuse across PM when Ca2+ rise in postsynaptic neuron
  • bind to presynaptic metabotropic receptors
  • reduce NT release at GABAergic synapses
37
Q

THC

A
  • agonist of CB receptors

- CB1 receptor highly expressed in basal ganglia: depression of activity in these areas = altered cognitive state

NESC 2570 (9 decks)

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