Lecture 16 Flashcards
Are neurotransmitters typically agonists or antagonists or both?
Agonists
Where are neurotransmitters synthesized?
In the terminal axon
Last 2 alternative fates of neurotransmitters regarding their removal from the cleft?
Degradation (e.g. AChE) or Reuptake (e.g. targeted by SSRI fluoxetine)
Typical types of postsynaptic neutortramistter receptors?
Nicotinic Acetycholine receptors; muscarinic receptors; Alpha 1, Beta-adrenergic receptors
What is the intracellular signal for the release of neurotransmitters into the cleft?
Calcium
How is the presynaptic cell returned to an inactive form?
Intracellular calcium gets sequestered, repolarizing the nerve terminal.
Which toxins act on neutrotransmitter vesicle release?
Botulinum toxin and tetanus toxin
How does tetanus toxin cause paralysis?
Prevents inhibitory neurotransmitters from being released, leaving excitatory signals to be released unopposed, resulting in rigid paralysis.
How does botulinum toxin cause paralysis?
Prevents release of ACh at the neuromuscular junction, which prevents muscle contraction from occurring (flaccid paralysis)
4 major ways neurotransmitters can be modulated by drugs:
- Modulate production of neurotramistter 2. Storage and vesicular release (depolarization, calcium entry, vesicle release)
- Modify affect of neurotransmitter (agonist and antagonists)
- Modify termination of the effect (metabolism/reuptake)
Examples of the 4 ways drugs modulate neurotransmission?
- L. Dopa provides precursor for L Dopamine in Parkinson’s patients. Is used to increase dopamine transmission.
- Blocking sodium channels (local anesthetics) prevents depolarization of neurons which ultimately prevents neurotransmitter release from nerve terminals.
- Agonists mimic effects of the endogenous neurotransmitter
- SSRIs prevent uptake of serotonin (fluoxetine)
What is presynaptic modulation of neurotransmission by drugs? Examples?
Auto-regulation and Cross-regulation.
Auto-regulation: when a neurotransmitter acts on its own nerve terminal to regulat its own release.
Cross-regulation: another neurotransmitter hormone acts on the nerve terminal to regulate its release of a neurotransmitter. Examples: Xylazine- an alpha-2 agonist, mimicking the effects of NE on the alpha2 receptors to decrease transmitter release; Cispramide and Metaclopramide are also pre-synaptic modulators that activate pre-synaptic serotonin receptors to cause an increase in ACh release and action on muscarinic receptors to increase GI movement.
Explain the concept of postsynaptic modulation by desensitization.
A postsynaptic receptor can be desensitized after prolonged stimulation. This often occurs after strong and long exposure to a drug. Nicotinic acetycholine re receptors (nAChR) undergo a conformation change causing them to lose function whereas Beta-adrenergic receptors get phosphorylated and internalized.
How can postsynaptic modulation of neurotransmitters lead to drug synergisms?
If two compounds are given together, they can have a much larger affect than either when given alone. This can officially between two neurotransmitters that have synergistic effects as well as between a neurotransmitter and a drug or between two drugs. For examples: Opiods and barbiturates or other CNS depressants have synergistic effects because opiods decrease excitatory transmission and barbituates increase inhibitory transmission. With both occurring at the same time, you can cause excess CNS depression.
What are co-transmitters? Examples.
Co-transmitters are molecules that are released which neurotransmitters (sometimes within the same vesicle).
Examples: ATP, Vasoactive Intestinal Peptide (VIP), Calcitonin Gene Related Peptie (CGRP)
