Phys Neurotransmitters Flashcards
What are the two types of neurotransmitter receptors?
Ionotropic (ligand-gated channels)
Metabotropic (G-coupled receptors)
What is an Ionotropic/ligand-gated raceptor?
Receptor activated by a ligand, any substance that can bind to a target protein
Describe Ionotropic/ligand-gated receptor mechanism
NT binds to the binding site of the post synaptic neuron -> channels open -> ions permitted to flow into the neuron -> change membrane potential -> send AP down neuron
Describe Metabotropic/G-coupled receptor mechanism
Is this mechanism slower/faster?
Specific/widespread?
NT binds to binding site -> activate G-protein -> can open ion channels or activate intercellular signaling molecules (secondary messengers) -> initiate signaling cascade within cell
Slower
More widespread
Which NT is the most abundant NT in brain/CNS and is involved in most every major excitatory brain function?
Glutamate
What are the two functions of Glutamate?
- Learning/memory
2. Synaptic Plasticity
What are the 2 main receptors glutamate binds to? Be specific
What is 3rd receptor it can bind to?
- Ionotropic: NMDA, AMPA, Kainate
- Metabotropic
Kainate receptors
When glutamate binds to ionotropic receptors, is it slow or fast transmission?
What are three functions?
-Fast transmission 3 functions: 1. Neuronal plasticity 2. Synaptic pruning 3. Apoptosis (controlled cellular death)
When glutamate binds to metabotropic receptors…
…what is it’s function?
…does it affect presynaptic or postsynaptic excitability?
Function - modulate glutamate release
Affect - postsynaptic excitability
Describe Kainate receptors affect on pre/post synaptic actions (which is Gaba and which is glutamate binding)
Presynaptic - GABA
Postsynaptic - Glutamate
Function of glutamate binding to Kainate:
- Less well known
- Minor role in synaptic plasticity (decrease affect of likelihood postsynaptic cell will fire in response to future stimulation)
What does a NT/drug that acts as an agonist do?
Binds to same receptors and have same effect as the NT
What does a NT/drug that acts as an antagonist do?
Block the effects of the NT
What does a NT/drug that acts as an inverse agonist do?
Bing to the sit the NT binds to and have the exact opposite effect
What does a NT/drug that acts as an neuromodulators do?
Binds to a site on the receptor that is separate from the site where the NT binds, and affect the likelihood that NT will bind
Phencyclidine (PCP) (Antagonist) will inhibit the reuptake of…
will inhibit the action of…
- Inhibit reuptake of dopamine, ne, and serotonin
- Inhibit the action of glutamate by blocking NMDA receptors
Initial impact of PCP -
Eventual impact -
Continued Usage -
Initially - less glutamate binding to receptors -> less APs (Relaxation, numbness, sensory distortions)
Eventually - excess glutamate overcrowding the synaptic cleft (confusion, agitation, analgesia, fever, schizo type behavior)
Cont’d usage - seizures, resp failure, coma, fever, stroke, death
What two ways does Riluzole decrease excess levels of glutamate in cases of ALS?
- Block release of glutamate from nerve cell
- Reduce glutamate vesicle fusion with the presynaptic cell membrane -> decrease amount of glutamate released into the synaptic cleft
Describe the clinical pathology of glutamate excitotoxicity
Increased glutamate -> continuous binding of AMPA and NMDA receptors and channels remain open for too long -> too much Ca++ ends up in cell -> apoptosis (cascade of cell death)
Describe positive/negative symptoms of Schizophrenia.
What are the two NT focuses on in this pathology?
Describe the possible pathology of SZ.
- Positive symptoms: delusions and hallucinations
- Negative: deficits, such as social withdrawal and lack of motivation
- Focus on dopamine and glutamate
- Possible pathology: NMDARs are hypofunctional
Describe the clinical pathology of epilepsy.
Describe what type of medication is used as anticonvulsants
- Excessive glutamate leads to overactive NMDA receptors -> thought to cause epileptic seizures
- Glutamate antagonists selective for NMDA or non-NMDA receptors are potent anticonvulsants
Describe the clinical pathology of Alzheimer’s Disease
What are the 2 primary symptoms?
- Excessive NMDAr activity -> excitotoxicity and promotes cell death
- Primary symptoms: memory deficits and inability to form new memories
What is GABA?
Is it excitatory/inhibitory?
Describe functions
- Gaba: major inhibitory NT in CNS
- Function:
1. Treats anxiety and used in rehab for drug abuse
2. Inhibits motor, sensory, and cognitive neurons -> sedation, muscular/cardiorespiratory, relaxation, pain inhibition
Describe the Ionotropic Gaba receptor:
GABAa or GABAb?
What ion does it control?
Describe mechanism of action
- GABAa found in nearly every neuron
- Controls Cl- entry into cell
- When Cl- enters cell, it will hyperpolarize making it harder for the AP to propagate
Describe the Metabotropic Gaba receptor:
GABAa or GABAb?
What ion does it control?
Describe mechanism of action
- GABAb will reduce muscle contraction
- Controls K+ out of cell
- When activated, cause opening of K+ channels -> K+ ions travel out -> hyperpolarize cell -> inhibits presynaptic release of NTs (ACh)
Describe the agonist action of Alcohol on GABA receptors (2 mechanisms):
Alcohol will increase GABA activity:
- Act on presynaptic neuron ->causing increase in GABA release (increase K+ out of presynaptic)
- Act on postsynaptic neuron -> facilitating activity of GABAa receptor (CL- into postsynaptic cell)
Describe the agonist action of Benzodiazepines on GABA receptors:
Used to treat what?
Affect pre/post synaptic?
- Psychoactive drug used to treat anxiety and insomnia
- Increase post synaptic receptors sensitivity to GABA binding
Describe the agonist action of Barbiturates on GABA receptors:
Used to treat what?
Affect pre/post synaptic?
- Sedation, decrease anxiety, and anticonvulsants for seizures
- Prolong opening of individual GABA operated Cl- channels
Describe the agonist action of Baclofen on GABA receptors:
Used to treat what?
Affect pre/post synaptic?
- Antispasticity
- Increase presynaptic release of GABA in spinal cord -> increase activity of GABAb receptors -> relaxation of muscles
Epilepsy treatment:
GABA agonists -
GABA antagonists -
Agonists - suppress seizures
Antagonists - produce seizures
Huntington’s Disease:
- Fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain
- Symptoms: personality changes, forgetfulness/impaired judgment, unsteady gait, involuntary movements (chorea - hallmark symptom), slurred speech, difficulty swallowing, and significant weight loss
1. Loss of NT (GABA, ACh, Glutamate) -> loss of neurons
2. Decrease GABA a receptors available in the brain
What is Glycine?
Where is it found?
Inhibitory/excitatory and pre/post synaptic response?
Describe mechanism (what type of receptor?)
- Glycine functions alongside GABA and is found in the brainstem and spinal cord
- Inhibitory post-synaptic response
Mechanism: when glycine receptors are activated -> Cl- enters the neuron via ionotropic receptors -> blocks AP
Describe Glycine antagonist Strychnine:
- Poisonous natural substance
- Used as pesticide
- Causes muscular convulsions and death by asphyxia
Describe clinical pathology of Spasticity
- Loss of inhibitory interneuron activity -> poorly coordinated muscle response -> spasticity
Describe clinical pathology of Spinal Shock:
Spinal shock - acute phenomenon seen after spinal cord injury
- Pt presents with LMN symptoms, despite UMN injury (low tone, absent reflexes,) that last hours to about 1 week
- Elevated levels of glycine found in SCI
Is Acetylcholine excitatory/inhibitory in pre/post synaptic neuron?
- Excitatory post-synaptic response
What are the functions of AcH
Functions:
- Triggers muscle contraction
- ANS involvement - slows HR, constricts pupils, increases digestive secretions and smooth muscle contraction
- Stimulates secretions of certain hormones
- CNS - wakefulness, attentiveness, anger, sexuality
What are the ionotropic and metabtropic receptors ACh binds to?
Excitatory or Inhibitory
Ionotropic - nicotinic (excitatory)
Metabotropic - muscarinic (excitatory or inhibitory)
- Regulation of cardiac muscle, smooth muscle, and glandular activity
What is the antagonist affect of Botulin Toxin?
- Inhibit ACh release into cleft
What are the 4 locations Botulin Toxins act on in the body?
- NMJ
- Autonomic ganglia
- Postganglionic parasympathetic nerve endings
- Postganglionic sympathetic nerve endings that release ACh
How is Botulin Toxins used as treatment? (2)
- Overactive smooth muscle
2. Abnormal activity of glands
Describe the use of Antagonist Atropine?
Blocks inhibitory effects of ACh on HR leading to Tachycardia (antagonist to muscarinic receptors)
Describe the use of Agonist Nicotine of the CNS?
- Increase ACh release -> enhanced cognition and attention
- Binds to nicotinic receptors and mimics ACh -> causes depolarization of post synaptic neuron
- Can cause increase dopamine levels in brain (addictive qualities)
Describe the use of Agonist Nicotine of the PNS?
- Increases sympathetic ns activity (increased HR and BP)
- Increase release of catecholamines like epi from adrenal glands -> increase SNS activity
Describe Alzheimer’s Disease and Dementia in regards to nicotinic receptors
- Loss of nicotinic-expressing neurons in the brain
Myasthenia Gravis:
What is it?
What symptoms?
Describe affect on nicotinic receptors
- Autoimmune disease, repetitive muscle use (eye and eyelids often) that leads to weakness
- Ptosis (dropping of eyelid) and strbismus (cross eyed apearance)
- Antibodies attack and destroy nicotinic receptors on muscle cells, so normal ACh but few receptors
Tabacco Addiction:
- Nicotine activates nAChR’s -> cause receptors to become desensitized -> brain upregulates (adds more) -> plays role in withdrawal and craving
Serotonin (5-HT):
Where is it found?
Excitatory/Inhibitory and pre/post synaptic?
- Found in the brain and brainstem (cluster of neurons called Raphe Nuclei)
- Excitatory and Inhibitory post-synaptic response
What are the functions of Serotonin?
- Emotions
- Sleep-Wake cycle
- GI Tract Regulation/ Appetite
- Cardiovascular growth factor (clotting)
- Increased -> can decrease sexual function
What are the ionotropic and metabotropic serotonin receptors?
Ionotropic - 5-HT3 excitatory
Metabotropic - 5-HT1-7 excitatory or inhibitory receptors
Describe role of agonist SSRIs
What are some examples?
Ex: Prozac, Zoloft, Celexa
- Increase levels of serotonin by inhibiting the reuptake
Describe serotonin’s role in depression
- Low levels of serotonin are linked to clinical depression
Describe serotonin’s role in Autism
45% of tested ASD subjects contained high levels of 5-HT in their blood
Describe serotonin’s role in serotonin syndrome
Signs and symptoms?
- High levels of serotonin as an adverse effect of serotonergic therapy
- Agitation, restlessness, confusion, tachycardia, HTN, loss of muscle coordination, muscle rigidity, heavy sweating
What is Dopamine?
Where is it found in the CNS and ANS?
- Amine function as neuromodulators
- Found in:
1. CNS: substantia nigra, midbrain, hypothalamus
2. ANS: sympathetic neurons
Is dopamine inhibitory/excitatory on pre/post synaptic?
Name some functions
- Excitatory and inhibitory on post-synaptic neuron Functions: 1. Drive 2. Attention, memory 3. Motor functions (extrapyramidal) 4. Addictive for narcotics
What are the ionotropic and metabotropic serotonin receptors?
Ionotropic - none
Metabotropic - excitatory and inhibitory
Describe Agonist Amphetamine on dopamine
- Bind to dopamergic receptors on presynaptic cell and enters -> increased release of dopamine into synaptic cleft
Describe Agonist L-dopa on dopamine
- Primary drug for parkinson’s
- L-Dopa (can cross BBB) is precursor to synthesis of dopamine (can’t cross BBB)
Describe Dopamine’s role in Parkinson’s
Where does PD develop in brain?
What are PD symptoms?
- Dopamine dysregulation in substantia nigra where cells begin to die
- Symptoms: resting tremor, rigidity, bradykinesia and loss of postural reflexes
Describe Dopamine’s role in Schizophrenia
What part of brain is affected for positive/negative symptoms?
- Recent studies suggest hypodopaminergic state in prefrontal cortex = negative symptoms -> leads to hyperdopaminergia in mesolimbic system and striatum = positive symptoms
Describe Dopamine’s role in ADHD
- Higher [ ] of dopamine transporters in brain -> remove dopamine from brain cells -> less time to exert its effects
Describe Dopamine’s role in Substance Dependency:
Acute
Chronic
Discontinuation of cocaine
Acute - increase synaptic dopamine because cocaine blocks presynaptic reuptake
chronic - down regulate dopamine receptors in response to overstimulation
Discontinuation - dopamine depletion and intense depression/agitation
Norepinephrine (noradrenaline):
Found in cortex and ANS -
Inhibitory/Excitatory on pre/post synaptic?
Found in:
- Cortex - locus ceruleus (pons), medulla
- ANS: sympathetic neurons (fight or flight)
- Excitatory post-synaptic response
What are the ionotropic and metabotropic norepinephrine receptors?
Ionotropic - none
Metabotropic - A1,A2 and B receptors (activation of B increase HR and force of contraction)
- Called adrenergic receptors
Describe beta blockers role on norepinephrine
- Bing b receptors -> prevent activation -> prevent increased NE (sweating, rapid HR)
- Can help with anxiety, HTN
Describe Amphetamines role on norepinephrine
- Increase blood and brain levels of NE:
1. Block reuptake
2. Increase its release from cells
Describe Cocaine’s role on norepinephrine
Block reuptake of NE
Describe Tricyclic antidepressants (TCAs) role on norepinephrine
Increase levels of NE and serotonin and block action of ACh
Describe NE on ADHD
- Increase brain levels of NE (but difficult to determine)
Describe NE on Hypotension
- Agonist activity on A1 and A2 causing vasoconstriction
Describe NE on PTSD
- Excessive NE in Veterans who experience PTSD
Describe NE on Parkinson’s
NE markedly decreased in various regions of PD brain
