Lecture 5 + 6 Flashcards
four categories of NT
amino acids, biogenic amines, neuropeptdes, nucleosides (lipids and gases)
two main examples of amino acid NT
Glu and GABA
biogenic amine NT
acetylcholine, catecholamines (dopamine and NE), seratonin
important neuropeptide NT
enkephalins
receptors are ___ coded proteins (embedded in plasma membrane)
genetic
three types of gating
ligand and voltage gated, as well as stretch
two basic types of receptors
ionotropic, metabotropic (tied to signaling)
respond to the transmitter released by their own nerve endings
autoreceptors (presynaptic) can regulate NT synthesis and release
NT catergory which has high conc. in brain and is fast, excitatory or inhibitory, short duration
amino acid
principal excitatory NT in nervous system, important in pain and long term memory
GLU
how is glutamate synthesized
byproduct of TCA cycle
high high levels of glutamate are
neurotoxic
glutamate can be made by ____ enzyme from glutamine in cell
glutanimase
VGLUTs pack NT (glutamate) into
synaptic vessicles
glutamate can be cleared by excitatory amino acid transporters (EAATs) on ____ ____ or by astrocytes (will not be recycled as NT, will be broken down to glutamine)
presynaptic terminal
SN1 and SAT2 are proteins which return glutamate to terminal where are they found?
plasma membrane only
glutamate has 4 different type of receptors (all are GLU gates cation channels)
NMDA, AMPA, kainate, mGluR
AMPA and kainate receptors pass primarily __ some _
Na, Ca
NMDA receptor primarily passes
Ca
___ is typically larger and faster out of the GLU channels
NMDA
___ blocks NMDA channels at hyperpolarized membrane potentials
Mg2+
things that have to happen for NMDA to open
- AMPA receptor has to turn on (changes membrane potential, gets rid of Mg)]
- GLU has to bind with a coagonist glycine
increase glutamate leads to neuronal death due to
excitotoxicity
most common inhibitory NT, synthesized by Glutamate
GABA
decrease of glutamate leads to
coma, death
GABA is packaged into vesicles by
VIAAT (vesicular inhibitory amino acid transp.
GABA is removed by ___ can be taken up by astrocytes or presynaptic cells converted to succinate
GATS
three types of GABA receptors dictated by subunits of receptor (bring in mainly Cl-)
a, b, c
regulation of GABA
benzodiaxepines, barbituates, steroids
NT category which regulate many brain functions, mostly behavior
biogenic amines
acetocholine is a ___ amine
quartenary
chatecolamines, histamine and seratonin are
biogenic amines
acetylcholine is synthesized by acetyl Coa and ___
choline
choline is taken up from environemnt by
ChT (choline transporter) 10,000 NT are loaded into vessicles
2 types of cholinergic receptors
muscarinic (cardiac and smooth) and nicotinic (skeletal muscle)
patients make autoantibodies that inhibit nicotinic Ach
myasthenia gravis
a treatment of myasthenia gravis is ____ its a competitive inhibitor
pyridostigmine
catecholamines are derived from
tyrosine
tyrosine is converted to ___ then to dopamine through use of dopa decarboxylase
DOPA
dopamine is converted to ___ through use of dopamine b- hydroxylase
NE
NE is converted to _____(E) through phenylethanol-amine-N-methyl tranferase
epinephrine
dopamine is found in ___ ____
corpus striatum (recieves info from substantia nigra, coordinates body movement)
dopamine is loaded into vesicles by
monoamine transporters
dopamine is cleared from synapse by and degraded by
dopamine transporters (DATS; on synaptic terminal and astrocytes) ; monoamine oxidase
seratonin is synthesized from
tryptophan –> 5-HTP
early form of antidepressants targeted
monoamine oxidase inhibitors
newer forms of antidepressants are called
SSRI’s or SNRI’s
NT category categorized by low conc. in brain and are typically modulators; receptors are metabotropic and slow
neuropeptides
neuropeptide made as pre-propeptides into active met and leu peptides
enkephalins
process of converting an extracellular signal to a functional change in cell
signal transduction
intracellular signaling involves ___
pathways
components of signaling pathway
signal, receptor, effector molecule, response
a molecule that binds to a specific site on another molecule
ligand
cells release a signal that initiates a transduction process in cells which recieve that signal
chemical communication
types of chemical communication
paracrine and endocrine signaling as well as synaptic transmission (NT)
ligands that cannot cross by themselves but need to bind to receptor
cell-impermeant molecules
ligand and receptor are both membrane bound and so cells must be close to have affect
cell associated molecules
must be able to distinguish between closely relates signals (receptor characteristic)
specificity
signal are often present in low conc. signal needs to bind well enough to cause cascade ,(receptor characteristic)
high affinity
cell has a finite number of receptors (receptor characteristic)
saturability
ligand-receptor linkage not covalent (need them to seperate) (receptor characteristic)
reversibility
receptor transfers a signal from outside to inside of cell (receptor characteristic)
coupling
4 types of receptors
channel linked, enzyme linked, g protein coupled, intracellular receptors
___ act as on-off switches
effectors (should to be transient; has on and off state)
g protein is made up of one monomer which gets turned on and off
monomeric g proteins
each subunit of effector is different and have different roles (ex. alpha can do signal, b and gamma can do regulation)
hetertrimeric g proteins
ras has two states (inactive bound to ___) in active state it is bound to __
GDP, GTP
___ helps to activate and exchange GDP for GTP
GEF
GAP do ___ to GDP
GTP
4 types of heterotrimeric G proteins
Gs (stimulatory) Gi (inhibitory) Gq (interacts with phospholipase C)
G12 (activate Rho GTPase)
makes cAMP+ ppi from ATP
adenyl. cyclase
makes cGMP+ ppi from GTP
guanylyl cyclase
both of cAMP and cGMP activate __ ___
protein kinases
___ _ cleaves PIP2 into IP3 and DAG
Phospholipase C
IP3 is broken down by ____ or made into other molecules
phosphotases
DAG is phosphorylated into ___ ___
phosphotidic acid
___ ___ form a pocket for protein to go into
catalytic subunits
need to have ___ to bind to catalytic subunits to disconnect from regulatory subunits which allows for comformational change
cAMP
in CAMKII the bond to Ca allows ___ ____ to extend away from association domain and can bind to proteins
catalytic subunits
in PKC (protein kinase C) ca allows lipid domain into plasma membrane ___ ___ is displaced and catalytic domain released
regulatory domain
