neurotransmitters

what defines a neurotransmitter

1. Synthesis: enzymes present in nerve terminal

2. Storage: in secretory vesicles

3. Release: regulated release into the synaptic space

4. Reception: presence of receptors

5. Removal: a means for terminating the action

life cycle of a typical transmitter

1. Synthesis

2. Storage/Packaging

3. Regulated Release

4. Detection/Signalling

5. Reuptake/Degradation

what are neurotransmitters

endogenous chemicals which transmit signals from a neurone to a target cell
across a synapse.

.basic signalling sequence

.presynaptic action potential

depolarisation of synaptic terminal

release of chemical transmitter

postsynaptic signal

small molecule transmitters

acetylcholine, amino acids, biogenic amines (catecholamines- dopamine, norepinephrine, epinephrine. also indoleamine- serotonin (5-HT). and imidazoleamine-histamine), pyrines and GABA

on a cholinergic synapse which releases acetylcholine what is the enzyme for synthesis

choline acetyltransferase (ChAT) catalyses acetyl coenzyme A and choline synthesized in the nerve terminals

on a cholinergic synapse which releases acetylcholine what is the enzyme for degradation

acetylcholinesterase (degradation) which is found in the synaptic cleft. has a high catalytic activity. the choline produced by this is recycled by being transported back into nerve terminals to resynthesize

what is glutamate

the central metabolic role in the brain

which transmitter does glutamate have a close metabolic relationship with

GABA

the main inhibitory neurotransmitter

GABA

the main excitatory neurotransmitter

the amino acid glutamate

how are neurotransmitters removed/degraded

either removed from the synaptic cleft by neurotransmitter transporters or by degradative enzymes

how does neurotransmitters affect the synapses

a neuron can be excited or inhibited and the postsynaptic response speed changes- control of electrical singalling over different timescales

the speed of small-molecule neurotransmitter vs biogenic amines and neuropeptides

biogenic amines and neuropeptides- slower, ongoing neuronal functions

small-molecule- rapid synaptic actions

where does glutamate get synthesised

it cannot cross the blood-brain barrier and must be synthesized in neurons from local precursors (e.g glutamine)

glutamine in the synthesis of glutamate

glutamine is taken up into presynaptic terminals by the system A transporter 2 SAT2 and is then metabolized to glutamate by the mitochondrial enzyme glutaminase

what are excitatory amino acid transporters

removes the glutamate from the synaptic cleft. Na+ dependent glutamate co-transporters. some are present in glial cells and others in presynaptic terminals

what transports glutamine out of glial cells

system N transporter 1 SN1 and transported into nerve terminals via SAT2

What are ionotropic glutamate receptors

AMPA and NMDA receptors- excitatory synapses

what are catecholamines derived from

the amino acid tyrosine

what catalyses catecholamine synthesis

tyrosine hydroxylase in a reaction requiring O2 and tetrahydrobiopterin to synthesize DOPA

where is dopamine found

mainly the corpus striatum which receives major input from the substantia nigra and plays an essential role in coordination of body movements. also produced in the ventral tegmental area in motivation, reward and reinforcement. plays a role in the sympathetic ganglia

how is dopamine produced

by the action of DOPA decarboxylase on DOPA in the cytoplasm of presynaptic terminals

how is dopamine transported

dopamine loaded into synaptic vesicles via a vesicular monoamine transporter VMAT

how is dopamine terminated

dopamine action in the synaptic cleft is terminated by reuptake of dopamine into nerve terminals or surrounding glial cells by a Na+ dependent dopamine co-transporter DAT

dopamine in parkinson’s disease

the dopaminergic neurons of the substantia nigra degenerate leading to a characteristic motor dysfunction

where is serotonin found

mostly in groups of neurons in the raphe region of the pons and upper brainstem which have widespread projections to the forebrain and regulate sleep and wakefulness

5-HT synthesis

from the amino acid tryptophan. tryptophan is taken up into neurons by a plasma membrane transporter and hydroxylated in a reaction catalysed by the enzyme tryptophan-5-hydroxylase

how is serotonin terminated

by transport back into nerve terminals via a specific serotonin transporter that is present in the presynaptic plasma membrane encoded by the SLC6A4