L20 Neurotransmitters Flashcards
What are the four general classes of NTs?
- small molecule transmitters - ACh and serotonin
- neuropeptides - CCK, substance P, VIP, orexin (vasopressin + oxytocin)
- gases - CO, NO
what is the life cycle of NT?
- synthesis
- nerve ending cytoplasm - small mole. NT
- in rER, Golgi and vesicles - neuropeptides
- in synap. vesicles - NE from DA
- storage in vesicles
- release
- binding to receptors
- degradation/re-uptake/reabsorption/diffusion
All NTs (with the exception of ACh, NO and peptides) are removed rapidly via _______ in the nerve ending by glial cells
transporters
*example - glutamate is taken up by neurons _ taken into astrocytes by their glutamate transporters. Glutamate is metabolized into glutamine which has its own transporter in neurons
DA, E, NE and serotonin are absorbed then broken down by ___ from the outer mitochondrial membrane in the nerve ending
MAOs
- there is also some degradation from COMT
- MAO and COMT are also present in astrocytes in liver
- some extracellular sites for MAO do exist.
what receptors do cholinergic neurons (ACh) use?
ionotropic - nicotinic
metabotropic - muscarinic
muscarinic M1, M3 and M5 have what type of response?
slow excitatory response - Gq–>PLC -> IP3 +DAG increase –> increase [Ca2+]
Muscarinic M2 and M4 have what type of responses?
inhibitory responses - Gi –> cAMP decrease –> closure of Ca2+ channels = weaker sponataneous depolarization
what are the major muscarinic subtypes in the brain (cerebral cortex + hippocampus)?
M1, M3, M4
what muscarinic subtype mediates gastric acid secretion?
M1
what type of actions do catecholamines (E, NE, and DA) have
both excitatory and inhibitory
what type of receptors do catecholamines use/
metabotropic only
where is DA important
CNS - parkinsons disease
no role in PNS
where is NE released from and what does it activate?
postganglionic sympathetic neurons
adrenoceptors in smooth n., glands and cardiac m.
where is E released from and what does it activate?
chromaffin cells
enters circulation and activates adrenoreceptosr
what isoproterenol?
synthetic form of epinephrine - similar in sutrcture to adrenaline (E), but has an additional CH3 group on the terminal N
where do dopaminergic cells in the substantia nigra project?
basal ganglia striatum (caudate nucleus + putamen)
D1 and D2 receptors on striatal neurons
where do dopaminergic neurons in the ventral tegmental area project?
hippocampus - new memory formation
nucleus accumbens
frontal lobe cortex - planning and attitude
how many receptors does DA have
5
what are the 2 families of DA receptors?
D1 - like (D1 and D5) - increase cAMP (excitatory)
D2-like (D2, D3, D4) - inhibit cAMP
what do postganglionic sympathetic neurons do to cardiac muscle?
excite!
what is the function of cardiac muscles beta 1 receptors?
increase cAMP - excite the HR and pacemaker
cardiac output increases in response to what stimulation?
sympathetic
what type of channels are AMPA/kainate and NMDA?
cation
describe the AMPA receptor
typical Na+ channel
describe the NMDA receptor
- blocked by residing Mg2+ which leaves under influence of very large depolarization (due to summation of many EPSPs)
- when it is unblocked it allows Ca2+ entry into the postsynaptic cell where the calcium plays a role in alterations of enzyme activity
what neurotransmitters mediate synaptic inhibition
glycine and GABA
what is the main inhibitory NT in the spinal cord
glycine
how does the glycine work in the spinal cord?
ionotropic receptor selective to Cl- - has similar structure to nAChR but NEEDS 3 MOLECULES OF GLYCINE TO OPEN CHANNEL!
how many molecules of glycine must bind to nGlyR?
3
what is the main inhibitory transmitter in the brain stem and brain?
GABA
what does GABAa receptor resemble
nAChR and glycine receptors - with two molecules of transmitter binding to alpha subunits before it can open!
how many molecules of GABA need to bind to GABAa receptor
2
what kinds of substances to glycine and GABA receptors bind?
anti-epileptic drugs, anti-anxiety drugs, sedatives, muscle relaxants, anesthetics
describe GABAb receptors?
metabotropic receptos - indirectly cause K+ channel opening through 2nf messengers - slow inhibition of postsynatpic neuron
how do benzodiazepines and barbiturates act on GABAa receptor channels?
-inhibition in the amygdala invovled with the development of fear and anxiety
where is the binding site on GABAa for benzos?
gamma subunit
where is the binding site on GABAa for barbiturates?
alpha and beta subunits
cholinergic neurons in the septal nuclei, basal nucleus of Myenert and pons connect to maintain ______, regulating a high level of consciousness
peak excitability
what do the ascending arousal system and cholinergic neurons also participate in?
raising levels of consciousness during REM sleep
amines and peptides have crucial roles in what
the CNS
the neurons in the locus ceruleus and rostral raphe nuclei innervate neurons in the
limbic lobe and cortex - mood, LO anxiety and optimism
when NE and serotonin transmission is low…
mood = feelings of despair, fear, anxiety
what does DA play a role in
depression and schizophrenia
what are brain dopamine receptors target in tx od
schizophernia, parkinsons disease and huntingtons chorea
dopamine receptor antagonist block what
- neuroleptics - block hallucinations and delusions
dopamine receptor agonists alleviate signs of what disease
-bromocriptine - sings of parkinsons disease
what therapeutic drugs are used to tx clinical depression
1- SSRI - slow upreg of serotonin receptors
- noradrenaline reuptake inhibitors
- MAO inhibitors - reduce degradation of NE and serotonin
what are the 3 endogenous opiod peptide families?
- beta endorphins
- enkephalins
- dynorphins
*they inhibit pain
what does substance P do
information about tissue damage and substance P mediates the increased pain sensation
what is capsaicin
in red hit chilli peppers - analgensic for pain = desensitize receptors and pain is reduced
prolonge capsaicin admin. downreg pain caused by death of primary afferent neurons = decreased release of substance P
what is the MOA for pilocarpine?
mimics ACh - agonist for muscarinic receptors of PNS
what is pilocarpine used to tx?
glaucoma - facilitates fluid drainage from eye via canal of Schlemm
what is the MOA for beta blockers
anatagonists of beta 1 receptors used to treat htn
what receptors do asthmatic bronchodilators work?
beta 2 agonist
what receptors do nasal decongestants work on
alpha 1 agonist = phenlephrine
