Neurotransmitters

• The nervous system coordinates our actions and sensory input, transmitting signals to and from different parts of our bodies.
• The nervous system is comprised of neurons and glial cells. Neurons are responsible for signal transmission - they have a unique structure for this purpose. Electrical signals (action potentials) propagate through neurons, stimulating the release of a chemical into the synapse. These chemicals are called neurotransmitters
• Neurotransmitters are the molecules involved in chemical transmissions
• Neurotransmitters are synthesised in the neuron and stored in synaptic vesicles.
• Synaptic transmission is unidirectional - the neurotransmitters are released from one neuron (presynaptic) into the synapse and bind to receptors on another neuron (postsynaptic). The type of response depends on the type of receptor. The neurotransmitter is then released from the receptor back in the synaptic cleft and removed (by reuptake, breakdown or diffusion)
• Specific neurotransmitters bind to different types of receptors. O
• One neurotransmitter can activate multiple different receptors/receptor subtypes
• Different receptors/receptor subtypes can be expressed in specific locations.
• Different receptor types have different modes of action
• LIgand-gated ion channels (ionotropic) - charged ions move in or out of the cell to make the cell more positively or negatively charged.
• Metabotropic (e.g. G-protein coupled) receptors - receptors activate intracellular signals that:

  • activate other intracellular signaling cascades (proteins/genes)
  • activate ion channels
• Classifications of neurotransmitters:

  • small molecules
  • amino acids (excitatory and inhibitory)
  • biogenic amines/monoamines (catecholamines, indoleamines, imidazole amines)
  • neuropeptides
  • gaseous molecules
• Receptor subtypes can be numbered or named for a selective ligand (often exogenous)
• Main peripheral receptors

  • acetylcholine (ACh)
  • nicotinic
  • neuromuscular junctions (N2)
  • autonomic ganglia (N1)
  • muscarinic
  • parasympathetic post-ganglionic (M1, M2 etc.)
  • sympathetic - sweating
  • noradrenaline
  • adrenoreceptors
  • sympathetic post-ganglionic (a1, B1)
  • presynaptic inhbitory (a2)
• GABA is the main inhibitory neurotransmitter.
• Glutamate is the main central excitatory neurotransmitter
• Endorphins/enkephalins inhibit nociception in the dorsal horn of the spinal cord
• Substance P amplifies nociception in the dorsal horn of the spinal cord
• Acetylcholine is responsible for motor function regulation (basal ganglia vs dopamine), emotion, arousal
• Dopamine is responsible for motor function regulation (basal ganglia vs ACh), regulation of hormone release (GH, prolactin)
• Noradrenaline is responsible for endorphin release int he spinal cord (inhibits nociception)
• Serotonin (5-HT) is responsible for endorphin release in the spinal cord (inhibits nociception)
• A 26 yo woman is having an elective (planned) caesarean section under spinal anaesthetic. This has the unwanted side-effect of lowering her blood pressure by blocking much of the sympathetic outflow from the spinal cord. This normally acts on blood vessels to produce vasoconstriction. What is the normal sympathetic neurotransmitter that acts on blood vessels?

  Noradrenaline
• A 26 year old woman is having an elective (planned) caesarean section under spinal anaesthetic. This has the unwanted side effect of lowering her blood pressure by blocking much of the sympathetic outflow from the spinal cord. This normally acts on blood vessels to produce vasoconstriction. To counteract this, phenylephrine is infused, which mimics the action of the sympathetic nervous system on blood vessels. What type of adrenoreceptor will this drug be stimulating?

  alpha 1
• A 2nd year medical student is about to go into the OSCE and has a tachycardia as part of the sympathetic response, brought about by catecholamine release from presynaptic stores. What type of adrenoreceptor is being activated?

  beta 1
• What enzyme regulates presynaptic stores of catecholamines?

  monoamine oxidase
• Into what class dose the beta 1 receptor fall?

  G protein coupled
• 28 yo male presents with persistent feelings of sadness, hopelessness and a lack of interest in activities which were previously enjoyed. Symptoms have been ongoing for 6 months and the patient reports a noticeable impact on daily functioning. Which neurotransmitter is associated with mood?

  Serotonin
• Which of the following drug type does not moderate the levels of serotonin?

  • MAOI
  • SSRI
  • SNRI
  • TCA
  • TMA-2KTO

  TMA-2KTO
• A patient with family history of Alzheimer's Disease mentions that she has read a newspaper article saying that nicotine can help prevent the disease. Which receptors do nicotine target?

  Nicotinic acetylcholine receptors
• Nicotine is thought to improve cholinergic function by activating nicotinic acetylcholine receptors. Galantamine is an AD therapeutic also designed to improve cholinergic function. What kind of drug is galantamine?

  Acetylcholinesterase inhibitor