neurotransmitter and receptors Flashcards
what are the 5 criteria of neurotransmitters
- in terminal
- Ca2+ dependent release
- subject to inactivation
- synaptic mimicry
- receptors exist
how are amino acid NT the workhorses of the CNS
- predominant type of NT
- 90% of synapases involve 4 AA - glutamate, aspartate, GABA, or glycine
whats the overall role of AA NT
can be excitatory (Glu, Asp) or inhibitory (GABA or Gly)
AA NT receptors
- most work through ionotropic (ion channel) receptors
- some use metabotropic receptors
AA NT inactivation
rapid uptake
- back into vesicle
- in glial cell - can stay there or go back to neuron
what is glutamate
- major excitatory NT
- widely distributed through the CNS
glutamate receptors
- ~13 types of receptors
- metabotropic - at least 8 varieties
- ionotropic - 3 major classes
what are the 3 major classes or ionotropic glutamate receptors
- NMDA
- AMPA
- Kainate
which ionotropic glutamate receptor is of the greatest interest and why
NMDA b/c it is heavily involved in learning and memory
What is GABA
- major inhibitory NT in CNS
- widely distributed through the CNS (important in inhibitory control of interneurons)
what is the name of the enzyme used to synthesize GABA
glutamic acid decarboxylase (GAD)
what are the two families of GABA receptors
- GABA(A) receptors
- GABA(B) receptors
GABA(A) receptors
allow Cl- ions into neuron resulting in membrane hyperpolarization
GABA(B) receptors
- G-protein coupled
- connected to K+ channels to cause membrane hyperpolarization
AA NT location importance
drugs acting on these transmitters/their receptors can exert GLOBAL effects on overall CNS function
what is increasing the overall INHIBITION of the CNS useful for
sedation, anethesia, anxiolytics, seizure control
- ketamine
- benzodiazepines and barbiturates (enhance GABA(A) receptor)
what is the enzyme used to synthesize acetylecholine
choline acetyletransferase
how is acetylecholine inactivated
acetylcholinesterase (breaks down ACh)
what are the two types of ACh receptors
- nicotinic Ach receptor (ionotropic)
- muscaromoc ACh receptor (metabotropic)
location of cholinergic neurons
specific circuits throughout brain
what are some CNS functions of ACh
- behavioral arousal
- attention
- REM sleep
- memory
- learning aggression
- grand mal seizures
- sensory perception
- energy conservation
- mood
- motor coordination
Ach is a prominent NT of the:
specific nervous system
autonomic nervous system
what is the action of acetylecholinesterase inhibitors
excessive buildup of ACh in the synapse is dangerous!
what are acetylecholinesterase inhibitors - irreversible inhibitors (organophosphates)
many products used in industry and agriculture (and war)
- insecticides
- poisonous gases
poisoning is very common
- physiologic excess of AChE exist in the body
- profound effects when 80-90% of enzyme is inactivated
- exposure is cumulative
- many agents penetrate skin
what is myasthenia gravis
an autoimmune disease with decreasing numbers of nicotinic receptors at neuromuscular junction
what are the 3 types of catecholamines
- dopamine
- norepinephrine
- epinephrine
what is a type of indoleamines
serotonin and melatonin
what is the catecholamine precursor
tyrosine
what is the rate limiting step and nonsecific decarboxylase of catecholamine synthesis
tyrosine 5-hydroxylase; aromatic amino acid decarboxylase
what are the enzymes needed to make norepinephrine and epinephrine
dopamine-B-hydroxylase; phenylethanolamine-N-methyl transferase
what is the rate limiting step in serotonin synthesis
tryptophan
what are the rate-limiting steps and nonspecific decarboxylase for serotonin synthesis
tryptophan 5-hydroxylase; aromatic amino acid decarboxylase
what are the rate-limiting steps in breakdown of catecholamines and serotonin and what is the same nonspecific enzyme? what is the additional enzyme needed for catecholamine breakdown
monoamine oxidase; aldehyde dehydrogenase; catechol-O-methyl transferase
what are the two MAO subtypes
MAO-A and MAO-B
preferences of MAO
- both subtypes capable of metabolizing all catecholamines and serotonin
- serotonin, norepinephrine, and epinephrine broken down by MAO-A
- dopamine broken down equally by both MAO-A and MAO-B
MAO is a ____ enzyme and is ____ the mechanism for removal of monoamines from the synapse
mitochondrial, NOT
catecholamine and indoleamine inactivation
rapid reuptake via specific transporters
dopamine: location and function
- hypothalamic regulation of hormones
- substantia nigra to basal ganglia play major role in movement
- midbrain projections to cortex and limbic system involved in schizophrenia, central “reward” pathway, working memory
what is parkinsons disease and how is it characterized
- progressive neurodegenerative disorder
- fatigue, lethargy, changes inmental alertness, tremors, bent posture, difficulty initiating voluntary movement
what does a marked loss of dopaminergic neurons in substantia nigra do
signs of parkinson’s disease
norepinephrine: location and function
- role in attention
- involvement with control of feeding
- connection to mood
- cell bodies of NE neurons reside in pons and medulla (locus coeruleus LC, lateral tegmental area LTA, dorsal medullary DM)
serotonin: location and function
- distribution in the body
- 90% present in the enterochromaffin cells of the GI tract
serotonin: location and function - CNS
- Raphne nuclei: all CNS serotonin is in the raphe and projects widely throughout
- fire in a highly regulated, pacemaker-like manner
what does the neuroanatomy and firing pattern of serotonin imply
broad homeostatic functions
what is the main function of serotonin
mood
what has low serotonin been associated with
- depression
- panic
- anxiety
- obsessive-compulsive behaviors
what is a drug used to tx low serotonin
Prozac - selective serotonin reuptake inhibitor (SSRI)
what do SSRI do
inhibiting SERT prolongs action of serotonin (5-HT) in synapse