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Pharmacology 3001 > Introduction to CNS - Kelly 2 > Flashcards

Introduction to CNS - Kelly 2 Flashcards

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1
Q

Blood brain barrier

A

Isolates CNS
Modified endothelial cells with light junctions: lipophilic things can pass, but ionic charged substances can’t
Lack of leakage
Astroglial process and pericytes
Highly lipophilic
BBB can be affected during injury or infection

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2
Q

Neuronal systems involved in

A 
Cognitive processing
Memory
Emotional processing
Sensory processing
Motor processing
Autonomic Processing
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3
Q

CNS neurotransmission

A

Depolarization at nerve terminal
Ca enters through channels
Promotes fusion of vesicles with nerve terminal to allow release
NT can be taken back or degraded

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4
Q

Sensitization of receptors

A

Sustained reduction in NT release or long term use of antagonist
Sensitized response when antagonist is taken away
Up regulation

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5
Q

Desensitization

A

Sustained blockade of NT reuptake or long term use of agonist
Receptor down-regulation: internalized

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6
Q

Important CNS receptors

A

Voltage gates
Ligand-gated ion channels
Membrane delimited metabotropic ion channel
Diffusible second messager metabotropic ion channel

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7
Q

Voltage gages ion channel

A

Ions moved based on what is favourable for voltage of cell
Pore is lined with charged amino acids
Voltage affects aa and they move to expose different areas
Facilitate opening that certain ions can move through

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8
Q

Ligand-gated ion channel

A

Inotropic channel

Channel is gated by binding of one, two or more ligands

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9
Q

Diffuse second messager metabotropic ion channel

A

Diffusible messenger activated ion channel

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10
Q

Excitatory membrane potential

A

Reaching AP
Conducted along axons and evoke NT release from nerve terminal
If enough EPSPs, AP will happen

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11
Q

Inhibitory membrane potential

A

Usually hyper polarizes the cell membrane and inhibits AP formation and can decrease NT release

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12
Q

Long tract cellular organization

A

Messages over long distances
Motor control
Relay, projection neurons

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13
Q

Local circuit cellular organization

A

Short, modulation
Shape recognition in the optic tract
Interneurons

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14
Q

Divergent

A

Widely projecting neurons
Global functioning
Sleep-wake cycles
Diffuse system

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15
Q

CNS neurotransmitters

A 
Amino acids
Acetylcholine
Monoamines
Peptides
Endocannabinoids
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16
Q

Criteria for a NT

A

Must be present in a higher concentration in the synapse than in other areas (localized)
Released by electrical or chemical stimulation via Ca-dependent mechanism
Produce a post-synaptic response similar to nerve stimulation (synaptic mimicry)
Mechanism for termination of transmitter action

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17
Q

Amino acids

A

High concentration in the CNS
Potent
Excitatory: glutamate
Inhibitory: GABA, glycine

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18
Q

Glutaminase

A

Converts glutamine to glutamate

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19
Q

Glutamate decarboxylase

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A

Converts glutamate to GABA

20
Q

Glutamate

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A

Major excitatory NT in CNS
Inotropic and metabotropic receptors
Termination by glia uptake, where it is converted to glutamine

21
Q

Inotropic glutamate receptors

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A

NMDAR, AMPAR, KAR

22
Q

Metabotropic glutamate receptors

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A

mGLUR1

Postsynaptic (Gq) and presynaptic (Gi)

23
Q

NMDAR

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A

Very calcium permeable when open
Reenforcement of Ca circuit
Do not like to be opened, at rest blocked by Mg
Need huge depolarization to be activated (summation)
Glu opens AMPAR non-selective ion channels which allows for further depolarization and dissociation of Mg

24
Q

GABA

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A

Inhibitory
Inotropic (GABAA, Cl) and metabotropic (GABAB, Gq)
Widely expressed
GABAB can be presynaptic
Ligand gated ion channel, binds between 2 subunits of pentameric structure
Allosteric modulators need orthosteric activity
Direct activation of K channel

25
Glycine
Inhibitory Inotropic (Cl) Limited expression: interneurons in SC and brainstem
26
Acetylcholine
``` Ionotopic (nicotinic) Metabotropic (muscarinic) Excitatory, inhibitory Widely expressed Cognitive functions Target in treatment of Alzheimers disease ```
27
Aceyltransferase
Convers AcCoA to acetyl choline
28
Muscarinic receptors
M1, M3, M5: Gq, increase IP3, DAG, decrease cAMP, gK | M2, M4: ion channel, increase gCa, gK, GNa
29
Monoamines
Dopamine, norepinephrine, serotonin (5-HT) Derived form aa Synthesis enzyme/neuron dependent Small amounts Complex functions: alertness, consciousness
30
Dopamine
``` 5 known receptors D1 or D2 Metabotropic Inhibitory Diffuse Target in Parkinson's disease L-Tyrosine to DOPA to dopamine Behaviour, drug reenforcement, emesis, hormone release, mood, motor coordination, olfaction ```
31
Tyrosine hydroxylase
Converts L-tyrosine to DOPA
32
L-amino acid decarboxylase
Converts DOPA to dopamine
33
D1, D5
Excitatory Gs, Gq Increase cAMP, IP3, DAG, Ca
34
D2, D3, D4
Inhibitory Gi/o Decrease cAMP, K, VDCC
35
Norepinephrine
Adrenergic receptors alpha and beta: metabotropic Excitatory Diffuse Attention, arousal Dopamine converted into norepinephrine by dopamine P hydroxyase Anxiety, learning, memory, mood, sensory, processing, sleep
36
Dopamine P hydroxylase
Converts dopamine to norepinephrine
37
A1 receptor (NE)
Gq | Increase IP3, DAG, Ca
38
A2 R (NE)
Gi | Decrease cAMP
39
B1, B2 (NE)
Gs | Increase cAMP
40
Serotonin
15 5-HT receptors (metabotropic) except 5-HT3 which is inotropic Tend to be inhibitory Diffuse Sleep, temperature, appetite, neuroendocrine control Target in treatment of affective disorders
41
Tryptophan hydroxylase
Converts tryptophan to 5-hyroxytryptophan, which is converted to 5-hydroxytryptoamine by LAAD
42
Neuropeptides
``` Many Opioids (endorphins, enkephalins) Pain sensation Target of analgesics, drugs of abuse Metabotropic Can be released in conjunction with other NTs Differ from non-peptide transmitters: 1. Synthesized in cell body and transported to nerve ending 2. No reuptake or enzyme degradation ```
43
Endocannabinoids
``` Rapidly synthesized and not stored Act on presynaptic receptors Cannabinoid receptor 1 Suppress NT release Memory, cognition, pain perception ```
44
Endocannabinoid signalling
Retrograde messaging Synthesized by Ca depended enzymes and released from postsynaptic neurons Signal travels retrogradely across synapse acting CB1R on presynaptic nerve terminal, inhibiting Ca channels Results in suppression of NT release
45
NO
Gas formed from arginine by NO synthase in CNS neurons | May participate in retrograde NT and LTP
46
Leptin/Orexin
Hormone modulators formed in hypothalamus | Important in regulation of appetite
47
Purines
Adenosine and ATP | activate specific purinergic receptors: evidence that ATP is a cotransmitter

Pharmacology 3001 (19 decks)

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