Receptors Flashcards
GABAa (11)
involved in chloride inhibition
post synaptic
formed from varying subunits 2a2by
6a subunits, 3b subunits, 3y subunits
BZDs dont work on a4-6 subunits
a5 subunit involved in memory
Binding site between a and y is BZDs
binding site between a and b is agonists/antagonists
channel blockers block the middle of the channel
allosteric modulators (barbiturates) are in the middle of the channel
channel modulators bind to the interior of the channel
GABAb (4)
pre and post synaptic
GPCR linked Gi/Go
K+ cascade
effected by GHB when in high concentrations
GHB (1)
stimulated in low concentrations of barbiturates and increases dopamine and alertness
AMPA (4)
post synoptic
must be activated before NMDA in order to remove Mg++
Glutamate receptors 1-4 are AMPA
ligand gated ion channel
Kainate (4)
pre and post synoptic
must be activated before NMDA in order to remove Mg++
glutamate receptors 5-7 are kainate
K1-2
ligand gated ion channels
NMDA (3)
post synaptic
heterotetrameric structure
ligand gated ion channel
a1 (6)
Gq
NA > A > IA
agonist - phenylephrine and methoxamide
antagonist - prazosine and dozazocine
PLC breaks PIP2 to IP3 and DAG causing Ca+ release
in charge of motor control, cognition and fear
a2 (6)
Gi
A > NA > IA
agonist - clonidine
antagonist - yohimbine and lolazoxan
inhibits sympathetic flow of CNS, decreases cAMP and Ca++ and increases K+
present in all CNS terminals
b1 (6)
Gs
IA > NA > A
agonist - dobutamine
antagonist - atenolol, and metaprolol
increases cAMP
present in cortex, striatum and hippocampus
b2 (6)
Gs
IA > A > NA
agonists - salbutamol, turbutaline, salmeterol and clenbuterol
antagonists - butoxamine
inhibits histamine release from mast cells and increases cAMP
found in the cerebellum
D1 (6)
Gs
agonist - dopamine
partial agonist - apomorphine and bromocryptane
antagonist - clorpromazine, haloperidol and clozapine
involved in reward pathways that produce Euphoria (Sibley 1999)
expressed highly in the cortex, limbic systems and striatum
D2 (6)
Gi/Go
agonist - dopamine, apomorphine and bromocryptane
antagonists - chlorpromazine, haloperidol, spiperone, roclopride
expressed highly in cortex, limbic system, striatum, ventral hypothalamus and anterior pituitary
present in chemoreceptor trigger zone in the medulla associated with N&V
decreased Ach increases K+ and decreases Ca++ which activates pre and post synpatic inhibiton
D3 (5)
Gi/Go
agonist - dopamine, apomorphine and bromocryptane
antagonist - spiperone, haloperidol and clorpromazine
high in limbic system, striatum, ventral hypothalamus and anterior pituitary
decreased Ach increases K+ and decreases Ca++ which activates pre and post synpatic inhibiton
D4 (5)
Gi/Go
agonist - dopamine, apomorphine and bromocryptane
antagonist - haloperidol, spiperone and clozapine
high in limbic system and striatum
decreased Ach increases K+ and decreases Ca++ which activates pre and post synpatic inhibiton
D5 (4)
Gs
high in limbic system and striatum
agonist - dopamine, apomorphine and bromocryptane
antagonist - clorpromazine, haloperidol and clozapine
I1 (2)
receptor for imidazoline
inhibition of sympathetic nervous system to decrease BP
I2 (2)
receptor for imidazoline
allosteric binding site on MAO - psychiatric association
I3 (2)
receptor for imidazoline
insulin secretion regulation
5-HT1 (6)
inhibitory
1A - widely distributed in the limbic system and is the major target for anxiety and depression meds
5-HT1A was found to control feeding behaviour by increasing appetite
1B and 1D - presynaptic inhibitory in the basal ganglia and cortex
5-HT1D antagonist sumatriptan - used for migraines
agonised by Bisporone as a treatment for anxiety
5-HT2 (5)
LSD acts upon it
inhibitory and excitatory by glutamate and GABA balance
2A and 2C - abundant in cortex and limbic system
Barnes + Sharp 1999 found that hallucinations and behavioural changes are by 5-HT2A
5-HT2 receptors have been found to decrease appetite
5-HT3 (4)
ligand gated ion channel (homo/heteromeric, Peters et Al 2005)
present in the area postrema causing vomiting
role of 3A and 3B is known Jensen et Al 2008
antagonised by ondansetron - use as an antiemetic
5-HT4 (3)
present in the limbic system, basal ganglia, hippocampus, substantia nigra
increased cognitive performance by increasing Ach release
receptors oppose respiratory depression actions in opioids
5-HT5 (1)
Baekaert et Al 2006 presented conflicting information on location and function
5-HT6 (2)
present in the hippocampus, cortex and limbic system
are targets for increased cognition and schizophrenia
5-HT7 (4)
LSD acts upon it
present in hippocampus, cortex, amygdala, thalamus and hypothalamus
found on axon terminals of GABAergic neurons
thermoregulatory systems, endocrine and mood, cognitive function and sleep
CB1 (4)
present centrally in the brain
peripherally in adipocytes, endothelial cells and peripheral nerves
Gi/o
most abundant form
CB2 (1)
works peripherally on immune cells as an anti-inflammatory
M1 (4)
Gq
present in the cerebral cortex
PLC - IP3 and DAG
increased cognition
M2 (3)
Gi
cardiac and widely distributed in CNS
decreased cAMP, neural inhibition and tremor
M3 (2)
Gq
smooth muscle and ocular accomodation
M4 (3)
Gi
CNS only
increased locomotion
M5 (2)
Gq
substantia nigra, salivary glands and ciliary muscles in the eye
Noradrenaline Pathways - location, function and drugs that utilise them (3)
Locus Coerulus to the cerebellum Locus Coerulus to the Cortex Locus Coerulus to hypothalamus Locus Coerulus to the hippocampus Locus Coerulus to the spinal cord
antidepressants, cocaine and amphetamines
arousal, blood pressure regulation and mood
Conditions involving dopamine (4)
Parkinsons
Schizophrenia
ADHD
Drug dependence
Locations of dopamine (4)
most abundant in the corpus striatum - motor system for coordination and movement
high also in frontal cortex
high in limbic system
high in hypothalamus
What differs a DA neuron from a NA neuron? (2)
dopaminergic neurons lack dopamine-B-hydroxylase
therefore it doesnt get converted into NA
Dopamine synthesis, reuptake, metabolism and elimination (4)
same pathway as NA for sytnehsis
reuptake by DAT
metabolism by MAO and COMT
COMT converts to DOPAC and HVA (which is an indicator of DA turnover)
released in urine as an indicator for DA release in body
Dopamine Pathways and their functions (7)
Nigrostriatial - 75% of dopamine neurons
Substantia Nigra - corpus striatum via the medial forebrain bundle
motor control
Mesolimbic
VTA (in pons cluster) - amygdaloid nucleus via the medial forebrain bundle
Behavioural control and emotion
Mesocortical
VTA to the frontal cortex
Tuberohypophyseal
Hypothalamus to the pituitary
Endocrine functions - inhibit prolactin release
Conditions involving 5-HT (6)
migraine
depression
anxiety
OCD
schizophrenia
drug abuse
5-HT functions (4)
sleep
appetite
thermoregulation
pain perception
5-HT synthesis (3)
PCPA can selectively and irreversibly inhibit Tyrptophan Hydroxylase
Availability of trytophan varies by food intake and time of the day as its derived by dietary protein
Tryptophan hydoxylases are the main factors to regulate synthesis
5-HT reuptake and metabolism (3)
SERT which is
inhibited by SSRIs
metabolised by MAO into 5-hydroxyindoleacetylaldehyde and then into 5-HIAA which is then excreted in urnie
5-HT pathways (8)
Rostral Nucleus to the basal ganglia
cortex
hippocampus
hypothalamus
cerebellum
spinal cord
medulla
limbic system
5-HT effects (4)
feeding behaviours
hallucinations
sleep and mood
control of sensory transmission - especially pain
effect of SSRIs on appetite - what is the significance (2)
decreases appetite
proves SSRIs inhibit 5-HT1 receptors more than 5-hT2 receptors
Why do hallucinogenic visions occur? (1)
loss of control of 5-HT pathways as these pathways normal function is to disregard irrelevant sensory informations
Name an SSRI and an anti-psychotic 5-HT drug (2)
SSRI - fluoxetine
anti-psychotic - clozapine
What is the effect of MDMA on 5-HT receptors (1)
competitively antagonises
Acetylcholine is found almost everywhere except where? (1)
cerebellum
What are the varieties of Ach receptor and how do the agonists and antagonists vary, and the paper that discovered it? (3)
(a4)2(B2)3 - agonist is nicotine and epibatidine
antagonist - mecamylamine
(a7)5 - agonist is epibatidine
antagonist - a-bungarotoxin and a-comotoxin
discovered by Gotti et al, 2008
Name non-selective muscarinic receptor agonists (3)
Acetylcholine
Carbechol
Bethanochol
Name the selective M1 agonist (1)
McNA343
Name the non-selective muscarinic receptor antagonists (5)
Atropine
Dicycloverine
Tolteridine
Oxybutinin
Hyoscine
Selective M1, M2 and M4 antagonists? (3)
M1 - pirenzipine, MT7 (mambo toxin)
M2 - galamine
M4 - MT3 (mambo toxin)
What conditions change the expression of nAchR’s (4)
schizophrenia
ADHD
depression
anxiety
Which parts of the brain do CB receptors effect and what is the result? (10)
Hippocampus - memory and amnesia
Cerebellum - disorientation
Hypothalamus - appetite and body temperature regulation
Substantia Nigra
Mesolimbic areas - reward
Cerebral Cortex
Explain the benefit of having limited CB receptors in the brain stem (1)
No serious cardiorespiratory toxic effects regarding their activation
CB receptors have been targeted therapeutically in 8 areas of the brain, what areas and why? (18)
Basal ganglia and cerebellum
treatment of motor function disorders
such as MS
Hippocampus
treatment for memory and learning disorders
Cerebral cortex
treatment of higher cognitive function loss
Hypothalamus
treatment of depression and obesity disorders
as CB has effects on thermoregulation, endocrine function and appetite
Amygdala
treatment of depression
emotion centre
Spinal Cord
treatment for peripheral sensation and chronic pain
Brain stem
to treat N&V as it has no specific area postrema receptors
cancer patients
Structure of nAchR’s (4)
pentameric
ligand gated cation channels
membres of the cys-lop superfamily
5-membrane spanning units form a central pore
What is the significance of nAchR heterogenicity? (4)
different subtypes have different sensitivity to nicotine
different rates of discovery and desensitisation
differ in Ca++ permeability
allosteric sites and phosphorylation capabilities
What are the functions of the brain regions?
Answer this
