CNS Neuropharmacology - French Flashcards
What is a hierarchical system? What is a diffuse system? What is the intent/goal of each?
Hierarchical systems exist to transmit information over long distances, such as motor control and sensory perception. These are the classic, myelinated pathways we think about as “nerves.” Disruption at any point destroys the signal. These systems contain relay neurons and local circuit neurons.
Diffuse systems exist largely to regulate hierarchical systems. They synapse over a broad swath of neurons, even crossing into functionally distinct parts of the CNS. They can affect vast CNS areas simultaneously subserving global functions: attention, sleep-wake cycle, appetite, emotions
What are local circuit neurons and relay neurons, and what part do they play in conduction? Which system (hierarchical/diffuse) do they comprise?
Relay neurons are generally excitatory (glu) and designed for delivery of longitudinal information.
Local circuit neurons are generally inhibtory (GABA) and are responsible for feed-forward and recurrent feedback loops.
Which neurotransmitters are generally involved in diffuse neuronal systems?
Ach
Monoamines (DA, NE, 5HT [serotonin])
GABA:
a. hierarchical/diffuse
b. List the precursors and key enzymes for their synthesis and transporters involved in their storage
c. Describe their synaptic inactivation mechanisms
d. Describe their receptors and signal transduction systems
a. Hierarchical.
b. Made from glutamate via GAD (glu. acid decarboxylase). Storage by VGAT.
c. Taken up by glial cells and converted to glutamine, then recycled into glutamate and reabsorbed by the neuron.
d. GABAa: Opens ligand-gated Cl- channel–>decreases neuronal excitability (IPSPs) [ionotropic]
GABAb: Gi/o inhibit adenylyl cyclase, decrease Ca++ conductance, open K+ channel
**GABA is the major neurotransmitter present in the CNS, scant amounts in the periphery
Which neurotransmitters are generally involved in hierarchical neuronal systems?
GABA (local circuit)
Glu (relay)
Glutamate:
a. hierarchical/diffuse
b. List the precursors and key enzymes for their synthesis and transporters involved in their storage
c. Describe their synaptic inactivation mechanisms
d. Describe their receptors and signal transduction systems
a. hierarchical
b. Glutamate [Glu] is formed from glutamine [Gln] by the action of glutaminase in the nerve ending. Newly synthesized glutamate is stored in synaptic vesicles for subsequent release
c. Reuptake as Glu, or uptake by glial cell, conversion to Gln, then transport to neuron/conv. by glutaminase
d. Ionotropic: AMPA, NMDA, Kainate (Na+ influx)
Metabotropic: R1-R5, R2-R3, R4-R6-R7-R8
**Responsible for almost all excitatory impulses in the CNS
Ach
a. hierarchical/diffuse
b. List the precursors and key enzymes for their synthesis and transporters involved in their storage
c. Describe their synaptic inactivation mechanisms
d. Describe their receptors and signal transduction systems
a. diffuse
b. made from acetyl-CoA by CAT (c. acetyltransferase) rate limiting step is the choline uptake (not CAT)
c. Packaged into storage vesicles for release by VAT. Released by VSCC (increases Ca conc.)
c. AChE (acetylcholinesterase)
d. Muscarinic receptors
M1-M3: Gq –> stimulate PLC activity
M2-M4: Gi/o –> inhibit adenylyl cyclase activity
Nicotinic receptors: NN opens receptor-gated cation channel [ionotropic]
Monoamines (catecholamines - DA, NE)
a. hierarchical/diffuse
b. List the precursors and key enzymes for their synthesis and transporters involved in their storage
c. Describe their synaptic inactivation mechanisms
d. Describe their receptors and signal transduction systems
a. diffuse
b. Synthesized from tyrosine (Tyr–> L dopa–> DA–>NE) 1st step is rate limiting
c. Storage by VMAT, storage protects from intraneuronal degradation by MAO, release by VSCC. REuptake is the primary inactivation. Each has a transporter [Dopamine transporter (DAT) Norepinephrine transporter (NET) Serotonin transporter (SERT)]
d. see separate flashcard (a1, b1, b2, a2, gs/io/etc)
VSSC vs VSCC
VSSC = voltage sensitive sodium channels VSCC = voltage sensitive calcium channels
Example: VSSC transmits AP to VSCC which causes vesicle fusion and release of ach, or catecholamines
α1 adrenergic: Gq/Gio/Gs? —> ?
Gq –> stimulation of phospholipase C activity
**PLC–>IP3–> Ca inward –> smooth muscle contraction
α2 adrenergic: Gq/Gio/Gs? —> ?
Gi/o –> inhibition of adenylyl cyclase
**Adenylyl cyclase–>cAMP–>pka–>Ca in (so inhibition would decrease Ca uptake in this situation)
β1 adrenergic: Gq/Gio/Gs? —> ?
β1 adrenergic: Gs –> stimulation of adenylyl cyclase activity
**Adenylyl cyclase–>cAMP–>pka–>Ca in (so inhibition would increase Ca uptake in this situation)
β2 adrenergic: Gq/Gio/Gs? —> ?
β2 adrenergic: Gs –> stimulation of adenylyl cyclase activity
**Adenylyl cyclase–>cAMP–>pka–>Ca in (so inhibition would increase Ca uptake in this situation)
