Neurotransmitter Systems Flashcards
Where is Ach located in PNS?
NMJ Autonomic preganglionic synapses Parasymp post-gang fibers Sympa post-gang fibers innervating sweat glands/muscle vasodilators Amacrine cells in retina
Where is Ach located in CNS (NOT part of ANS)?
Striatum (motor control)
Brainstem arousal system (peduculopontine tegmental & laterodorsal pontine nuclei)
Basal forebarin arousal system
Involved in producing arousal (non-specific increase in cortical activity produced by sensory info arriving @ brainstem arousal systems)
Synthesis & release & catabolism of Ach
acetate & CoA combined to make Ach
moved into vesicles by VAchT
broken down by acetylcholinesterase (choline taken up by presynaptic cell & acetate diffuses away)
Ach receptors
muscarinic: smooth muscle cells & glands
nicotinic: NMJ & neuronal
Location & G protein assoc of Ach muscarinic receptors
M1 (post gang neurons of ANS & in CNS)-Gq
M2 (cardiac)-Gi (increases K+ conductance)
M3 (smooth m of bronchi & vasc)-Gq
M4 (presynaptic autoreceptors controlling Ach release & striatum of basal ganglia for motor control)-Gi
M5 (cerebral vasc & basal ganglia dopaminergic neurons for motor control)-Gq
What are the 5 subunits of the Ach nicotinic receptor?
alpha subunit beta subunit gamma subunit sigma subunit e subunit
What does the change in subunit in the nicotinic receptor affect?
decreases the open time of channel but increases sodium entry (larger conductance)
What is Stiff Person Syndrome associated with?
increased muscle rigidity & muscle spasms associated with decreasing GABA content (autoimmune disorder)
What produces and releases GABA?
pancreatic beta cells produce GABA from glutamate using GAD
Where is GABA located in the CNS?
cerebellum & cortex
What is main mechanism of removal of GABA from synapse?
reuptake via specialized transport protein & NaCl co-transport w/ GABA
How is GABA metabolized?
GABA transaminase to succinic aldehyde to succinate
enzymes in pre synapse
GABA a receptor
chloride channel that results in IPSP b/c influx of chloride
increased Cl conductance w/ alpha subunit binding
other metabolites potentiate its effects & produce sleep/drowsiness
GABA b receptor
metabotropic receptor coupled to heterodimer G protein
decrease in AC that leads to increase in K INFLUX to hyperpolzarize cell
interacts w/ Gq system that decreases IP3/DAG & decrease in Ca2+ influx
GABA c receptor
ionotropic (Cl-) & found in retina
How do anesthetics work with GABA receptors?
CNS has lots of GABA receptors that are extrasynaptic so general anesthetics can activate them & increase level of inhibition (leads to loss of awareness)
Where is glycine located in the CNS?
Spinal Cord
Retina, brainstem, forebrain
What is the receptor for glycine?
ionotropic Cl- channel (blocked by strychnine)
alpha subunit binds ligand of glycine
Where are purine NTs located in peripheral nervous system?
sympathetic nerves parasympathetic nerves sensory nerves intrinsic nerves of gut & heart motor nerves
Where are purine NTs located in brain?
cortex hippocampus cerebellum basal ganglia midbrain thalamus brainstem
What is the main difference between ATP & Adenosine as NTs?
ATP works on receptors that are largely post-synaptic & adenosince works on receptors that are largely pre-synaptic
Why is adenosine considered a 2nd messenger?
not the secreted NT (broken down from ATP to ADP to AMP to adenosine)
How are purine NTs removed from synaptic cleft?
reuptake of adenosine & adenosine deaminase in cleft creates ionsine which can be removed by circulation
What receptor does adenosine bind?
P1 receptor
metabotropic that increase or decrease cAMP production
What receptor does ATP bind?
P2X receptors
all 7 are ionotropic (cations) that allow Na+ or Ca2+ or oth to flow in
What receptor can both ATP & ADP bind?
P2Y receptor (higher affinity for ADP)
all metabotropic receptos that lead to Gq activation
What are the functions of adenosine?
sleep induction
feedback inhibition of ATP release
What are the functions of ATP or ADP?
modifying action of main NT released from presynaptic terminal
maintenance of LTP for producing long term memory
modification of NT release (GABA, norepi, ACh, glutamate & other excitatory AAs)
What is the location of opioids in CNS?
striatum (basal ganglia) hypothalamus periaquaductal gray nucleus parabrachialis raphe nuclei in brainstem
What are the precursor molecules for opioids?
Proenkephalins
Pro-opiomelanocortinins
Prodynorphins
Nociceptin
Where are prodynorphins localized?
hypothalamus
thalamus
brainstem
retina
What is unique about metabolism of opioid NTs?
all is enzymatic (likely after reuptake)
Enkephalinase A (splits Gly-Phe bond) Enkephalinase B (splits Gly-Gly bond) Aminopeptidase (splits Tyr-gly bond)
What are the 3 types of receptors for opioid NTs?
Mu
Kappa
Delta
all are serpentine receptors assoc w/ Gi to inhibit AC & indirectly alter other ion flows
What is the Mu opioid receptor assoc w/?
analgesia
respiratory depression
euphoria
increases K efflux-hyperpolarization
What is the kappa opioid receptor assoc w/?
analgesia
dysphoria
decrease in Ca2+ influx
What is the delta opioid receptor assoc w/?
analgesia
decrease in Ca2+ influx
Where does the arachidonic acid for both AEA & 2AG NTs come from?
arachidonic acid is from cell membrane
How is anadamide metabolized?
primary enzyme is fatty acid amide hydrolase (FAAH)
if reduced activity, reduced nociception (esp for heat)
How is 2AG metabolized?
monoacyl glycerol lipase
Where is the CB1 located?
most abundant G receptor in brain (Gi)
found on presynaptic terminals in CNS & PNS
in the CNS: hippocampal formation, basal ganglia, neocortex, cerebellum, spinal cord
What are the effects of binding CB1?
decrease NT release
predominance of EAA inhibition may be possible (endocannabinoids interact w/ both EAA & GABA NT systems)
What NT is predominant at human neocortex?
EAA
higher # of GABA receptors expressed extrasynpatically (on cell body)
Spinal cord CB1 receptors
assoc w/ modification of nociceptive inputs
Neocortical CB1 receptors
assoc w/ neuroprotection against excitotoxicity
Hippocampal & basal ganglia CB1 receptors
assoc w/ changes in affect
Where are CB2 receptors located?
brain (microglia)
immune syste
gut
What are CB2 receptors in brain tied to?
inflammatory processes in brain (MO remove B-amyloid)
What are CB2 receptors in immune system tied to?
lymphocytes, thymus, spleen & tonsils
modify cytokine release (anti-inflammatory)
What are CB2 receptors in gut tied to?
wide spread expression of GI tissue (treatment of inflammatory bowel disease)
