Lecture 9+10 +DLA 14 Flashcards
(52 cards)
traditional criteria for neurotransmitters
- synthesized by presynaptic neurons
- stored in preparation for release
- released by presynaptic neurons in a Ca dependent way
- have a special receptor
- mechanism for removal from synapse
Dopamine transport and removal (catecholamine)
- dopamine is synthesized from tyrosine
- Reuptake-1 actively transports DA into presynaptic neuron
some is loaded into vesicles and some is metabolized by MAO - Reuptake-2 actively transports DA into the postsynaptic neuron for metabolism by COMT
Remaining synaptic DA diffuses and is absorbed by blood for peripheral metabolism
norepinephrine transport and removal (catecholamine)
- DA enters the vesicle and is converted to NE by dopamine beta hydroxylase
- Reuptake-1 actively transports NE into presynaptic neuron
Some NE reloaded into vesicles
Remainder metabolized by MOA - Reuptake-2 actively transports NE into postsynaptic cell for metabolism by COMT
Remaining synaptic NE diffuses and is absorbed by blood for peripheral metabolism
epinephrine transport and removal (catecholamine)
- NE leaks into the cytoplasm where is is converted to epinephrine by PNMT
- Reuptake-1 actively transports epinephrine into presynaptic neuron
Some E reloaded into vesicles
Remainder metabolized by MOA - Reuptake-2 actively transports epinephrine into postsynaptic cell for metabolism by COMT
Remaining synaptic epinephrine diffuses and is absorbed by blood for peripheral metabolism
serotonin (indolamines)
synthesized from tryptophan
Serotonin actively transported into vesicles for storage and then release
Synaptic serotonin can undergo reuptake or metabolism by monoamine oxidase to 5- hydroxy-indoleacetyldehyde
Aldehyde dehydrogenase then converts 5-
hydroxy-indoleacetyldehyde to 5-hydroxyindoleacetic acid for urinary excretion
synthesis and removal of glutamine (AA neurotransmitter)
synthetic pathway 1:
Krebs cycle (alpha oxoglutarate transaminase yields glutamine)
starts with glucose
synthetic pathway 2:
glutamate recycling
glutamine is converted to glutamate by the astrocytes and neurons working together; can go through vesicular reloading
synthesis and removal of GABA (AA transmitter)
Glutamine can be converted to GABA
(glutamine to glutamate to GABA)
after release GABA receptors can reuptake and glia can take up GABA to form glutamine
synthesis and removal of glycine (AA transmitter)
Glycolysis of glucose yields 3- phosphoglycerate and subsequently serine
Serine transhydroxymethylase folatedependently converts serine to glycine
Membrane-spanning transporters take up synaptic glycine
synthesis and removal of ACh
Choline retrieved from the synapse interacts with acetyl coenzyme-A in presence of ACh transferase to yield ACh
ACh enters vesicles
ACh esterase hydrolyzes ACh (choline can be taken up for reuse)
low molecular weight synthesis of transmitters
synthesized in the cytosol
load into vesicles (small and clear)
vesicles are tethered awaiting release
high molecular weight synthesis of transmitters
propeptides synthesized in the somata
loaded into large dense-core vesicles with cleaving enzymes
peptide-containing vesicles are stored farther from release sites compared to the small clear vesicles
synthesis, removal, and function is histamine
histamine is derived from histidine by histidine decarboxylase
removed by histamine methyltransferase and diamine oxidase; forms acids and excreted in urine
function:
can be inhibitory or excitatory
The hypothalamic tuberomammillary nucleus
the major aggregation of histamine producing neurons
innervate cortex, hypothalamus, posterior pituitary, cerebellum, medulla, and spinal cord (histaminergic)
H1 receptors
increase excitability by suppressing activity of potassium channels
excitatory
H2 receptors
receptor activation stimulates protein kinase activation which inhibits calcium activated potassium channels
excitatory
H3 receptors
receptors are negatively coupled to adenylate cyclase. Subunits of the G-protein also suppress voltage-gated calcium channels to decrease transmitter release
inhibitory
beta endorphin
synthesis:
arises from anterior and intermediate pituitary and the arcuate hypothalamic nucleus (RER)
degraded by peptidases
inhibitory at most synapses in the medulla and spinal cord
(opioid peptides are important in pain regulation)
Enkephalins
originate from spinal and caudal bulbar neurons
degraded by peptidases
inhibitory at most synapses in the medulla and spinal cord
substance P
Synthesized in peripheral unmyelinated nociceptive
fibers
Released into spinal dorsal horn and spinal nucleus of the trigeminal nerve
inhibited by serotonin and norepi
degraded by peptidases
inhibitory and excitatory
electrical synapses
synchronize electrical signal activity among cells
mediated by cap junctions
voltage sensitive
intracellular communication
chemical synapses
most common
neurotransmitters are released into the synapse to lead to a reaction.
synapses can change to mediate learning
what are the different kinds of chemical synapses?
axodendritic = influence likelihood of AP at target cells
axosomatic = often reduce probability of AP at target cell
axoaxonic = diminish magnitudes of AP’s and thus reduce transmitter release
ACh receptors: ionotropic and metabotropic
ionotropic = nicotinic
change in ion flux (Na, K)
rapid effects
metabotropic = muscarinic metabolic changes (phosphorylation) slow effects
metabotropic receptors
receptor couple to G-proteins
ligand binds and dissociates alpha subunit
alpha subunit can be both excitatory and inhibitory
effects on ions channels, metabolism, gene expression
