Neurotransmitters (M2) Flashcards
when is acetylcholine (ACh) utilized
in synapses within the cns and pns
cholinergic neurons
neurons that utilize ACh as the primary neurotransmitter
cholinergic synapse
synapse employing ACh
choline acetyl transferase (ChAT)
enzyme that synthesizes ACh within the synaptic vesicle of the presynaptic cell
what is acetyl CoA formed from
acetate and coenzyme A (CoA) by a synthetase enzyme
what does botulinum toxin bind to
SNARE proteins, which prevents vesicles from releasing excitatory ACh
acetylcholinesterase (AChE)
enzyme that does enzyme degradation of ACh in the synaptic cleft
4 processes involved in removing neurotransmitters from the synaptic cleft
- reuptake of NT into the presynaptic cell via active transport and repackaged into vesicles
- uptake of NT by surrounding glial cells
- diffusion of NT away from synaptic cleft
- enzymatic degradation of NT (ex. acetylcholinesterase)
what does ACh bind to within the cholinergic synapse
nicotinic (nicotine-binding) or muscarinic (muscarine-binding) receptors of the postsynaptic cell
are nicotinic receptors ionotropic or metabotropic? excitatory or inhibitory?
ionotropic
excitatory
are muscarinic receptors ionotropic or metabotropic? excitatory or inhibitory?
metabotropic
excitatory or inhibitory
location of nicotinic receptors
somatic effectors (skeletal muscle) at neuromuscular junctions within somatic nervous system.
ganglionic neurons at their synapse with preganglionic neurons in the autonomic ganglia of the ANS.
chromaffin cells of the adrenal medulla.
in postsynaptic cells within spinal cord gray matter of cns
location of muscarinic receptors
autonomic effectors (cardiac and smooth muscle, glands except sweat) at its synapse with parasympathetic ganglionic neuron (postg.) in ans.
autonomic effectors (sweat glands) at its synapse with sympathetic ganglionic neuron (postg.) in ans.
postsynaptic cells within gray matter in various areas of the brain of the cns.
ACh and alzheimer’s
neurons associated with ACh system degenerate in people with Alzheimer’s.
decreased amount of ACh in certain areas of the brain and even the loss of the postsynaptic neurons that would have responded to it.
these defects are related to the declining language and perceptual abilities, confusion, and memory loss that characterize alzheimer’s victims.
structure of catecholamines
6-carbon ring with 2 hydroxyl groups (catechol) plus an amine group and formed by uptake of amino acid, tyrosine, into axon terminal
what originates from tyrosine
dopamine
norepinephrine (noradrenaline)
epinephrine (adrenaline)
where are cell-bodies of catecholamine-releasing neurons located
within hypothalamus and brainstem of cns.
- few in number, but the axons of these neurons branch significantly and project to virtually all areas of the brain and spinal cord.
what do catecholamines exert
essential functions on consciousness, mood, attention and movement, blood pressure, and hormone release
where are epinephrine and norepinephrine synthesized besides its synthesis in axon terminals
medulla of adrenal gland –> also classified as hormones
monoamine oxidase (MAO)
enzyme that degrade catecholamines
MAO inhibitors
increase amount of dopamine and norepinephrine by slowing their degradation
what does dopamine bind to
dopaminergic receptors (metabotropic)
where are dopaminergic receptors found
mostly in the cns.
present to a lesser degree in the pns.
does dopamine act as a neurotransmitter or hormone
can act as a neurotransmitter or travel through the blood and act on other cells as a hormone
effects of dopamine
reward and motivation.
blood pressure and fluid regulator.
affects secretion of other hormones.
where are adrenergic receptors found
located on autonomic effectors (cardiac and smooth muscle, glands) at its synapse with the sympathetic ganglionic neuron (postg.) in the ans
what do adrenergic receptors bind
catecholamine neurotransmitters norepinephrine and epinephrine
are adrenergic receptors metabotropic or ionotropic? exert excitatory or inhibitory effects?
metabotropic.
exert excitatory or inhibitory effects on postsynaptic cell.
second messenger pathways can vary by adrenergic receptor type.
what are the adrenergic receptors
alpha-adrenergic receptors: alpha1 and alpha2.
beta-adrenergic receptors: beta1, beta2, beta3.
norepinephrine effects on adrenergic receptors
can work on alpha-adrenergic and beta-adrenergic receptors.
impacts on beta-adrenergic receptors are not as robust as with epinephrine
epinephrine effects on adrenergic receptors
can work on alpha-adrenergic and beta-adrenergic, but more robust response when bound to beta-adrenergic than norepinephrine
what are indolamines
second subclass of the biogenic amine neurotransmitters
what is the structure of serotonin and location
5-hydroxytryptamine or 5-HT.
found in vast majority of brain and spinal cord structures (CNS) and derived from amino acid tryptophan.
also made by enterochromaffin cells in the gut and taken up and stored in nerve terminals and platelets.
what does serotonin exert excitatory and inhibitory effects on
exerts excitatory effect muscle control and inhibitory effect on pathways that mediate sensation.
levels lowest during sleep and highest during alterness
what are SRIs
serotonin reuptake inhibitors.
believed to aid in management of depression (ex. paroxetine = Paxil).
what is histamine misclassified as
indolamine.
it is a biogenic amine - derived from the amino acid histidine, which does not have an indole group in its chemical structure.
main cns location of serotonin
brainstem
functions of serotonin
regulating sleep.
emotions (obsessions, compulsions).
memory.
appetite/weight changes.
5-HT3 receptors in the medulla of the brainstem (‘area postrema’) are involved in vomiting reflex.
regulates cell growth.
vascular smooth muscle cell contraction.
general knowledge about parkinson’s disease
involves the loss of dopamine-releasing neurons in the substantia nigra of the midbrain which affects motor contol.
cause of disease is not clearly understood, loss of dopamine neurons is critical.
symptoms of parkinson’s disease
persistent tremors.
head nodding and pill rolling behaviors.
forward bent walking posture.
shuffling gait.
still facial expressions.
slow in initiating and executing movement.
what are symptoms of parkinson’s disease managed with
the drug L-Dopa (precursor to dopamine) in the initial stages to alleviate symptoms and often concomitantly prescribed with the drug deprenyl (prevents L-Dopa degradation)
experimental treatments for parkinson’s
deep brain stimulation by surgically implanting electrodes, and gene therapy
qualities and examples of amino acids that act as neurotransmitters
short-acting.
glutamate.
aspartate.
glycine
what is glutamate and where is it found
primary neurotransmitter at 50% of the excitatory synapses in the cns.
most common in cns; synthesized in mitochondria from glucose and glutamine
types of glutamate receptors
ionotropic glutamate receptors: very active and one of the major cellular processes in learning and memory.
- AMPA receptors (bind to alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid).
- NMDA receptors (bind N-methyl-D-aspartate).
Metabotropic glutamate receptors
qualities of AMPA ionotropic glutamate receptors
fast EPSP.
conduction of Na+.
qualities of NMDA ionotropic glutamate receptors
at resting membrane potential, NMDA channels are blocked by Mg2+.
AMPA receptor EPSPs change membrane potential by 20-30 mV is enough to bump Mg2+ from NMDA channel, allowing for influx of Ca2+.
Important in exocytoxicity.
what is glutamate recycled by and what happens
recycled by glial cells and converted into glutamine for reuptake by presynaptic cell
what is GABA
gamma-aminobutyric acid.
most common inhibitory neurotransmitter - dampens neural activity in the brain.
derived from an enzymatically-modified form of glutamate.
what does GABA bind to and what happens
binds to ion channels and cause immediate change in membrane potential to a more negative charge as Cl- channels are open
what do GABA receptors possess
additional binding sites that serve as targets for steroids, ethanol, and drugs including barbiturates and benzodiazepines (Xanax, Valium)
what are GABA receptors
GABA sub A (ionotropic).
GABA sub B (metabotropic)
what is glycine converted by and what is it
converted from serine by an enzyme.
inhibitory neurotransmitter of the brainstem and spinal cord.
how does glycine cause an IPSP
increases Cl- influx into the postsynaptic cell like GABA.
why is glycine important
acts on spinal integration centers of the spinal cord that regulate skeletal muscle contraction
what is strychnine
glycine antagonist.
causes hyperexcitability through the nervous system leading to convulsions and spastic contraction of skeletal muscles (spastic paralysis)
what are neuropeptides
amino acid chain.
maybe made as a precursor molecule.
stored in dense core vesicles.
modulate responses.
growth factors, hormones
why is nitric oxide different from the classic neurotransmitters
not stored in vesicles.
synthesized on an ‘as needed’ basis in the postganglionic neurons and released from these cells that can act on preganglionic neurons (retrograde) to release additional neurotransmitters
what happens to nitric oxide in the postsynaptic cell
synthesized from the amino acid arginine in a Ca2+/calmodulin-dependent manner and catalyzed by the enzyme NO synthase
what does nitric oxide activate
cGMP - second messenger
functions of nitric oxide
vasodilation.
long-term potentiation (memory).
what is too much nitric oxide
proinflammatory and can be cytotoxic
nitric oxide isoforms
nNOS
eNOS
iNOS
what are the metabolically active molecules
carbon monoxide (CO).
hydrogen sulfide (HS).
purines: ATP and adenosine
what are endocannabinoids synthesized and released from
postsynaptic cells
what do endocannabinoids do
decrease neurotransmitter release from presynaptic neurons.
alter memory and cognition.
increase appetite.
what are anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG) and what do they bind to
endocannabinoids.
bind to CB1 and CB2 cannabinoid receptors.
what is tetrahydrocannabinol and what does it bind to
active ingredient in marijuana.
can bind to CB1 and CB2 receptors.
what can a drug do
- increase leakage of neurotransmitter from vesicle to cytoplasm, exposing it to enzyme breakdown.
- increase transmitter release into cleft.
- block transmitter release.
- inhibit transmitter release.
- block transmitter reuptake.
- block cleft enzymes that metabolize transmitter.
- bind to receptor on postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action.
- inhibit or stimulate second-messenger activity within postsynaptic cell.
