amino acid transmitter pharma Flashcards
what are the amino acid neurotransmitters
glutamate, GABA, glycine
how is glutamate synthesised and transported into vesicles
glutamate derived from food and metabolism in cells
taken up from extracellular space by reuptake via excitatory amino acid transporters (EAAT1-5)
concentrated into vesicles in glutamatergic neurones via vesicular glutmate transporter (VGLUT)
how is GABA synthesised and transported into vesicles
synthesised from glutamate by glutamic acid decarboxylase (GAD)
taken up from extracellular space by reuptake via GABA transporters (GAT1-4)
concentrated into vesicles in GABAergic neurones via vesicular inhibitory amino acid transporter (VIAAT)
how is glycine synthesised and transported into vesicles
taken up from blood or synthesised by all cells
taken up from extracellular space by reuptake via glycine transporters (GlyT-1and2)
concentrated into vesicles in glycinergic neurones via VIAAT
(some neurones release both GABA and glycine)
describe the structure of LGIC glutamate receptors
tetrameric
contain 3 transmembrane alpha helices labelled M1-4
M2 does not cross membrane entirely but is a loop that enters intracellularly and leaves intracellularly
L-glutamate is agonist of glutamate receptors, D-glutamate is not
describe AMPA receptors
GluR1-4
causes increase in sodium/potassium flux
describe NMDA receptors
NR1, NR2A, NR213, NR2C, NR2D, NR3
causes increase in sodium/potassium/calcium flux
normally blocked by magnesium. depolarisation of membrane causes unblocking, relief of Mg block leads to further depolarisation, voltage gated
presence of extracellular glycine is necessary for activation (co-agonist)
what types of kainate receptors are there
GluR5-7 and KA1-2
cause increase in sodium/potassium flux
describe metabotropic glutamate receptors
mGluR1-8
3 groups of mGluR
group 1: mGluR 1 and 5, excites phospholipase C causing increase in IP3 and DAG (Gq)
group2: mGluR2 and 3, inhibits adenylyl cyclase, Go
group 3: mGluR4 and 6-8, also causes inhibition of adenylyl cyclase, Go
(group 2 and 3 differ in agonist selectivities)
describe ionotropic GABA receptors
GABAa has variety of subunits (alpha1-6, beta1-3, gamma1-3, delta, epsilon, pi, tau and rho1-2)
pentameric LGIC
causes increase in intracellular chloride
GABAc also LGIC
describe metabotropic GABA receptors
GABAbR1-2
opens potassium channels causing decrease in intracellular potassium
reduces intracellular calcium and cAMP
Gi/o
may be pre or post synaptic receptors,
pre synaptic GABA receptors reduce calcium concentration
postsynaptic cause efflux of potassium from cell
describe glutamate metabolism
alpha-ketoglutarate is converted to glutamate via glutamate dehydrogenase
alpha-ketoglutarate is produced by citric acid cycle
glutamate is converted to glutamine via glutamine synthase
glutamine is converted to glutamate via glutaminase
name modulators of GABAa receptors
benzos, barbiturates, steroids, alcohol, anaesthetics
benzos are positive allosteric modulators of GABAa receptors
describe GABA metabolism
glutamate is converted into GABA via glutamic acid decarboxylase
GABA is converted into succinic semialdehyde via GABA transaminase