Chemical Messengers and Excitotoxicity Flashcards
Difference between ionotropic and metabotropic NTs
Ionotropic = FAST — increase conductance to certain ions by binding ligand-activated channels
Metabotropic = SLOW — act to alter membrane properties via second messenger (often GPCRs)
What are the 5 biogenic amine (monoamine) NTs
Catecholamines = epinephrine, norepinephrine, dopamine
Histamine
Serotonin
Synthesis of catecholamines from tyrosine and RL step
Tyrosine —> L-DOPA (RL step) (requires tyrosine hydroxylase)
L-DOPA—> dopamine —> NE —> Epi
NE—> Epi requires PNMT
Dopamine is stored in vesicles in neurons. ____ work to move dopamine, epi, etc. into specialized storage vesicles
VMATs
Predominant mechanism for inactivation of Epi released by adrenal medulla, but also present in CNS
COMT
Which NT’s neurons are located in locus ceoruleus and project to nearly every part of CNS?
Norepinephrine
Functions of NE
Crucial to waking up and awareness
_____ is used by a small fraction of neurons in the CNS and is primarily released by adrenal medulla
Epinephrine
Where are the neurons that produce dopamine?
Substantia nigra
Ventral tegmental area of midbrain
4 major systems that use dopamine
Substantia nigra — motor
Mesolimbic — VTA to nucleus accumbens. Central to pleasure, reward, addiction
Mesocortical — VTA to frontal cortex. Attention, high-level consciousness
Tuberinfundibular — hypothalamus to AP. Supresses release of prolactin
Where is histamine found
Tuberomammillary nucleus (TMN) of posterior hypothalamus
Function of histamine
Wakefullness
Which histamine receptors mediate neuronal effects?
H1 and H2
What degrades histamine
Diamine oxidase
Serotonin neurons are located where?
Raphe nuclei
Derivation of serotonin
Tryptophan —tryptophan hydroxylase—> 5HTP (RL)
5HTP —5-HT decarboxylase—> serotonin
Function and metabolism of serotonin
Controls attention and mood; involved in depression
Metabolized by MAO enzyme after uptake
How many serotonin receptors are there? Are they metabotropic or ionotropic?
7
All are metabotropic associated with GPCR signaling except 5-HT3 which is ionotropic
Function of 5-HT2A
Smooth muscle contraction
Function of 5-HT3
Vomiting
Function of 5HT6
High affinity for several antidepressants
Function of 5HT2C
Plays a role in controlling normal body weight and preventing seizures
Central location of acetylcholine (cholinergic NT)
Pons
Midbrain
Motor cortex
[peripheral locations = autonomics, NMJ]
Location of ACh neurons
Basal forebrain complex, which includes septal nuclei and nucleus basalis
[others originate in pontomesencephalotegmental cholinergic complex]
Function of ACh
Learning, memory, producing consciousness, voluntary motion, REM sleep
Transport mechanism for ACh from cytosol into vesicles
VAChT
Where is acetylcholinesterase found?
Bound to post synaptic cell membrane
Which ACh receptors are ionotropic vs. metabotropic?
Nicotinic receptors are ionotropic
Muscarinic receptros are metabotropic
Inhibitory amino acids
GABA
Glycine
Location of GABA
Cortex, cerebellum (higher brain centers)
Synthesis of GABA
Glutamate —glutamate decarboxylase—> GABA
GABA tranmission is limited by ______. It is catabolized by __________ enzyme into succinic semialdehyde (SSA)
Reuptake; GABA-transaminase
GABA receptors
GABA(A) = most prevalent, conducts chloride (IONOTROPIC), benzodiazepine receptor
GABA (B) = GPCR (METABOTROPIC), results in increased K+ conductance or decreased Ca conductance
Main inhibitory NT in spinal cord
Glycine
3 opioid peptides
Endorphins
Enkephalins
Dynorphins
4 types of receptors for opioids
Mu = analgesia, increases K efflux
Kappa = analgesia, decreases Ca influx
Delta = analgesia, decreases Ca influx
Nociceptin = hyperalgesia
