Neurotransmitter Classification Flashcards
neurotransmitters are classified based on
- chemical nature
- response they elicit
- their receptors mechanism of action
how is the activity of a neurotransmitter changed?
regulated by changing the rates of synthesis and release at the synapse, and by blocking reuptake and degradation
what is the endocannainoid system
a group of endogenous cannabinoid receptors located in the mammalian brain and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors
list criteria necessary to be a nt
- synthesis in the neuron
- storage within nerve ending
- release in response to stimulus
- bonding and recognition at post synaptic cell
- mechanism for inactivation and termination of activity
name some neuromodulators
- NO
- adenosine
- neurosteroids
- polyamines
- lipids
how are nt released?
(A) In the resting state, vesicles are attached to microtubules.
(B) When an action potential is received, calcium channels open. (C) Vesicles move to the plasma membrane, and (D) bind to a complex of docking protein
(E) Neurotransmitter is released, and
(F) vesicles are recycled
name amine nts
Ach, norepinphrine, epinephrine, dopamine, 5-HT
name amino acid nts
glutamate GABA
Name purine nts
ATP, adenosine
name gase nts
NO
name peptide nts
endorphons, tachykinins
name lipid nts
anandamide, 2-AG (arachidony glycerol)
excitatory nts
Acetylcholine Aspartate Dopamine Histamine Norepinephrine Epinephrine Glutamate Serotonin
inhibitory nts
GABA
Glycine
Anandamide
2-AG
fast mode nts use
ionotropic receptors
modulatory mode nts use
GPCR (metabotopic receptors)
how is Ach synthesized
in cholinergic neurons, by choline acetyltransferase. you need choline and acetyl coA as reactants
where is Ach released and why
Motoneurons at the level of the neuromuscular junction (muscle contraction)
Pre-ganglionic neurons of the sympathetic nervous system and parasympathetic post-ganglionic neurons (slowing of the heart rate, bronchoconstriction, stimulation of intestinal smooth muscle)
Neurons of the reticular system (wakefulness, sleep-wake transition)
Cholinergic synapses of basal ganglia (learning, memory)
what are the 2 cholinergic receptors
- nicotinic (ionotropic):
- Nm depolarization of NMJ
-Nn activation of post ganglionic neurons - muscarininc receptors (metabotropic)
-M1: Depolarization of autonomic and CNS neurons
– M2 Negative inotropic and chronotropic effects on the heart
– M3 Stimulate sweat, bronchial, salivary and gastric acid secretion; increase NO production from vascular endothelium and vasorelaxation
how to remove Ach from synaptic cleft
- ACh released from synaptic vesicles is hydrolyzed to choline and acetate by acetylcholinesterase (AChE), an enzyme that is localized in the synaptic cleft. Choline is a poor binder of the cholinergic receptors, however is taken up by the uptake system on the presynaptic membrane
- The remainder of ACh (i.e., that has not been hydrolyzed by acetylcholinesterase) is taken back up into the pre-synaptic nerve by specific transporters (reuptake).
explain ACHe
is an enzyme which hydrolyses Ach, its active site contains 2 subsites. An anionic subsite to bind Ach to the enzyme. The esteratic subsite where the hydrolytic action occurs, releasing acetate and choline
list the 3 ionotropic glutamate receptors
AMPA
NMDA
KAINATE
GABA-a receptors are
ionotropic, and ligand gated Chloride channels
GABA-b receptors are
metabotropic
benzodiazepines bind to
GABA-a, cause a potentiation of the response to endogenous GABA; these drugs reduce anxiety and also cause muscle relaxation
barbiturates bind to
GABA-a, stimulate them directly in the absence of GABA; because of this lack of dependence on endogenous ligand, they are more likely to cause toxic side effects in overdose.
how is GABA re-uptaken?
by plasma membrane transporters (symports):
GABA transporters 1-3 (GAT-1, GAT-2, GAT-3) Betaine-GABA transporter-1 (BGT-1) (GAT1-3 in brain, BGT-1 mostly in kidney but also present in brain)
where is glycine found?
what does it do?
what kind of receptor is it?
- inhibotry nerons in spinal cord
- where it blocks impulses travelling down the cord in motor neurons
- ionotropic. And is blocked by strychinine. They are ligand gated chloride channels.
all catecholamines (dopamine, nor-/epinephrine) are derived from?
tyrosine.
They are biogenic amines. They are released through varicosities along the axon not only the end of it.
where is epinehrine produced
adrenal medulla
L-DOPA in melanocytes is the precursor or
melanins
norepinephrine is the major transmitter in
sympathetic nervous system, in post ganglionic neurons. for fight or flight. Also in the brainstem, for overall awareness or attention (locus ceruleus)
amphetamines
have stimulatory effects since they increase the concentration of catecholamines in the synaptic cleft
epinephrin traits
- influences heart, lung
- redirection of blood to skeletal muscle
- stimulatory effects on glycogen metabolism in liver
- is not essential for life
dopamine traits
- nerves that interconnect the nuclei of the basal ganglia in the brain and control voluntary movement
- damage causes parkinsons
- schizophrenia
- causes vasodilation and used for treatment of renal failure
- found in the nigrostriatal tract
how are catelcholamines catabolised?
- half life of 1 min
- Monoamine oxidase (MAO): catecholamines by oxidative deamination to yield the corresponding aldehyde.
Catechol-O-methyltransferase (COMT) also inactivates catecholamines by methylation using S-adenosylmethionine (SAM) as the one-carbon donor.
MAO inhibitors and methamphetamine block catecholamine degradation, allowing their accumulation in the presynaptic neuron and subsequent leakage into circulation, providing an antidepressant action.
serotonin
aka 5-HT
- Trp hydrolase need cofactor BH4
- 5-HT is converted to serotonin by DOPA decarboxylase
- in raphe nuclei, more active when awake
- involved in feeding, sexual behavior, temperature
how is serotonin broken down?
- oxidation by monoamine oxidase
- dehydration: aldehyde deydrogenase
NO
- in ANS and enteric NS is made from arginine by BH4 NOS.
- excessive NO= alzheimers and parkinsons
- is not stored in vesicles but released immediately
