1.3.1 CNS Neurotransmitters Flashcards
Describe the synthesis of serotonin.
– made from tryptophan → 5-HT
Some drugs can do what to histamine receptors?
-Inhibition of histaminergic receptors is responsible fro the sedative adverse effects of many drugs
What is the synthesis of Dopamine?
tyrosine → DOPA → Dopamine
What is the synthesis of Norepinephrine?
from tyrosine → DOPA → dopamine → NE → Epi
What are some examples of indirect gating?
- Gs: stimulates AC
- Gi: inhibits AC & opens K channel
- Gq: stimulates phospholipase C
- Go: closes Ca channel
What are the characteristics of chemical synapses?
- Slower and more complex signaling than electrical synapses
- Important for the function of most CNS active drugs
What is the importance of glutamate?
most predominant excitatory NT in CNS
Drugs that target opoid receptors are used for?
-Drugs targeting opioid receptors are used to treat pain
What are the receptors for glutamate?
NMDA (blocked by Mg)
AMPA (pain)
kainate
GPCR
Describe the synthesis of GABA.
-Formed by decarboxylation of glutamate
What is indirect gating in regards to chemical synapses?
- Indirect Gating: Non-Channel Linked Receptors
- Binding of nt activates second messenger pathways via G-proteins (metabotropic)
How is acetylcholine synthesized?
- Combination of acetyl CoA (from mitochondria) and choline (from diet)
- Catalyzed by choline acetyltransferase (ChAT)
Describe the termination of GABA
Reuptake
How can stimulants and amphetamines affect the action of norepinephrine?
Amphetamines - can cause increased release of norepinephrine
Stimulants (cocaine) - cause decreased reuptake of norepinephrine
How is norepinephrine terminated?
Reuptake
What is the sequence of events in a chemical synapse?
- Release of NT from pre-synaptic terminal requires calcium
- Voltage-dep calcium channels open when AP depolarizes them
- Transmitter diffuses through synaptic cleft to post-synaptic neuron
- Post-synaptic response depends on the type of receptors present
What are the receptors for norepinephrine?
Adrenergic
α1-excitation, increased IP3:DAG
α2 – inhibitory at pre-synapse
β- GPCR (increased cAMP)
Alzheimers disease is related to cholinergic action?
- reduction in the activity of cholinergic neurons
- drugs are used in AD to increase cholinergic activity
What are the characteristics of nuclear receptors?
- Binding of a ligand to a nuclear receptor will cause a downstream change in gene expression
- This modulation of gene expression may be either to up or down regulate transcription
What is the role of serotonin?
- Serotonergic mechanisms modulate anger, aggression, body temp, mood, sleep, human sexuality, appetite and metabolism
- Also have potential to stimulate emesis
What are the receptors acetylcholine and what is their importance?
- Muscarinic – Metabotropic receptors important in glandular secretion (M1 is excitatory and M2 is inhibitory)
- Nicotinic – Ionotropic receptors important in motor end plate function (increased conductivity to cations)
How is the effect of acetylcholine terminated?
- Metabolism by acetylcholinesterase (AChe) on postsynaptic membrane (choline recylced)
- Very short half life
What are some examples of neurotransmitters that utilize direct gating?
- Glutamate
- ACh
- GABA
- Glycine
- Serotonin
What is the effect of serotonin on the different receptors? (Dont know if this is important)
- Receptors
- Metabotropic:
- 5-HT 1A– Inhibitory
- 5-HT 2A – Excitatory
- Ionotropic:
- 5-HT 3 – Excitatory
- ↑ cation conductance
- 5-HT 4 – Excitatory
- ↓K conductance
What is the role of dopaminergic receptor activation?
- Dopaminergic receptors are responsible for reward and motivation, as well as many emotions like euphoria, orgasm, anger, addiction, love, and pleasure
- Also important in the regulation of renal vascular flow
Decreased GABA can lead to?
-Decreased GABA activity or increased glutamate activity can precipitate seizures (ex: in alcohol withdrawal)
What is direct gating in regards to chemical synapses?
- Direct Gating: Ligand-Gated Receptors
- Binding of neurotransmitter opens or closes an ion channel within the receptor (ionotropic)
- Activation results in a rapid change in postsynaptic membrane potential
What are the characteristics of synaptic transmission?
- Bridges synaptic gaps between neurons and their target cells
- Rapid cell communication and long-term modulation
- Drugs have enormous impact on this process
What is the role of GABA?
-Major inhibitory neurotransmitter in the brain
What is the role of histamine outside the brain?
-Histaminergic mechanisms are critical in peripheral inflammation (H1) and gastric acid secretion (H2)
D2 (dopamine) receptor activation leads to?
- D2 Receptors: inhibitory
- Mechanism of effect depends on the location of the receptor:
- Presynaptic: ↓ Ca Conductance
- Postsynaptic: ↑K → ↓cAMP
Glutamate over-excitation is involved in?
-Glutamatergic over-excitation of neurons is involved in both acute and chronic brain injury (high ca influx)
SSRIs target what?
-reuptake transporters on presynaptic membrane
What are the characteristics of gap junctions?
These are also electrical synapses
Extremely rapid cell communication
Links activity between adjacent cells
Drugs have minimal impact on this process
What is acetylcholine?
Small nt released (Ca- dependent) in vesicles at presynaptic terminal, crossing synapse, and binding to cholinoceptors on postsynaptic membrane
What is the use of adrenergic receptors?
- Adrenergic receptors elevate mood and increase wakefulness and attention
- Also have critical CV functions
