Neurotransmitters Flashcards

1
Q

What proportion of prescriptions are made up of CNS active drugs?

A

1 in 6.

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2
Q

Outline the synthesis of noradrenaline from tyrosine.

A

Tytrosine, (tyrosine hydroxylase) L-Dopa, (L-aromatic amino acid decarboxylase) Dopamine, (dopamine beta hydroxylase) Noradrenaline.

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3
Q

Which step of the synthesis of noradrenaline is the rate limiting step?

A

The first step.

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4
Q

What is L-DOPA used to treat? How does it work?

A

L-DOPA is used to treat Parkinson’s Disease as this disease is caused by a lack of dopamine. L-DOPA is favoured over dopamine itself as dopamine can’t pass across the blood brain barrier; L-DOPA can so it is used and is then converted to dopamine.

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5
Q

What is noradrenaline stored in?

A

Dense cored vesicles 70-200nm in diameter.

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6
Q

How does Reserpine modulate noradrenaline action?

A

Reserpine blocks the proton gradient dependent pump that transports the amines into these vesicles. If NA can’t get back int the vesicles then it remains in the synaptic cleft and is broken down by enzymes, whilst also providing greater stimulation. The enzyme that breaks down NA is called monoamine oxidase (MOA).

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7
Q

Define quanta.

A

Quanta is defined as the amount of neurotransmitter released in one vesicle.

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8
Q

Outline the release of noradrenaline.

A

The release occurs by a process of exocytosis in which synaptic vesicles fuse with the presynaptic membrane and release their contents into the extracellular space.

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9
Q

Describe both of the two uptake mechanisms used in noradrenaline inactivation.

A

There are two uptakes; uptake one involves reuptake into neurones and uptake two involves reuptake into non-neuronal elements such as glial cells.

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10
Q

Give the characteristics of noradrenaline uptake 1.

A

Low capacity, high affinity. 75% uptake. Takes up other substrates suych as dopamine and 5-HT (serotonin). Inhibited by cocaine, amphetamine, and tricyclic antidepressants.

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11
Q

Give the characteristics of noradrenaline uptake 2.

A

High capacity, low affinity. 25% reuptake. Inhibitd by normetanephrine and steroid hormones.

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12
Q

Give a preferred agonist, perferred antagonist, and the mechanism for alpha 1 adrenoreceptors.

A

Phenylephrine. Prazosin. K+ conductance.

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13
Q

Give a preferred agonist, perferred antagonist, and the mechanism for alpha 2 adrenoreceptors.

A

Clonidine. Yohimbine. Ca2+ conductance.

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14
Q

Give a preferred agonist, perferred antagonist, and the mechanism for beta 1 adrenoreceptors.

A

Isoproterenol & Dobutamine. Metoprolol. K+ conductance.

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15
Q

Give a preferred agonist, perferred antagonist, and the mechanism for beta 2 adrenoreceptors.

A

Salbutamol. Butoxamine. NO pathway.

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16
Q

How does the action of alpha 1 adrenoreceptors, K+ conductance, have an effect.

A

Potassium is blocked from leaving the cell, preventing hyperpolarisation, leading to net excitation.

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17
Q

How does the action of alpha 2 adrenoreceptors, reducing calcium conductance, have an effect.

A

When the receptor binds with NA, it negatively impacts the conversion of ATP to cAMP. This reduces the amount of cAMP available to phosphorylate calcium channels, preventing calcium influx needed for calcium dependent exocytosis.

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18
Q

Define an autoreceptor and give an example.

A

Autoreceptors are where the receptor recognises the transmitter that is released from that terminal. E.g. alpha 2 adrenoreceptors.

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19
Q

Define a heteroreceptor and give an example of an inhibitory heteroreceptor and a facilitatory heteroreceptor.

A

Heteroreceptors are where the receptor recognises other transmitters which are different from that which is released from that terminal. Inhibitory = opiate/histamine/muscarinic. Facilitatory = angiotensin II.

20
Q

Give the function consequences of dopamine in the brain.

A

Motor control, behavioural effects, and endocrine control.

21
Q

What symptoms does a lack of dopamine cause in Parkinson’s disease?

A

Bradykinesia (slow movement) and akinesia (no movement).

22
Q

How is Schizophrenia associated with dopamine?

A

Schizophrenia is caused by a patient having too much dopamine.

23
Q

What are the brain loci for dopamine releasing cells?

A

The substantia nigra and the mesolimbic pathways (shown in orange) are the locations of the dopamine releasing cells.

24
Q

How is dopamine inactivated?

A

Active reuptake.

25
Q

How are animal models of Parkinson’s generated?

A

6-HAD can be injected into the substantia nigra to kill off the dopaminergic neurones. This leads to there being no movement, known as catalepsy. If only one side of the brain is affected, then the animal suffers from collateral turning – turning towards the side of the lesion.

26
Q

What are the CNS effects of 5-HT (seratonin)?

A

Hallucinatory behaviour, feeding behaviour, control of mood and emotion, control of sleep/wakefulness, control of sensory pathways increasing nociception, control of body temperature, vomiting.

27
Q

What are the 5-HT loci in the brain?

A

The rostral Raphe nuclei and the caudal Raphe nuclei (in orange) are the location of the 5-HT nerves. Most parts of the brain, including the higher centres of the brain, have 5-HT innervation.

28
Q

Outline the synthesis of 5-HT from tryptophan.

A

Tryptophan, (tryptophan hydroxylase) 5-hydroxytryptophan, (L-aromatic amino acid decarboxylase) 5-HT.

29
Q

How many types of 5-HT receptors are their? Are there subtypes? If so, how many on average?

A

There are seven types of 5-HT receptors with many having A-D subtypes.

30
Q

Give a preferred antagonist, the mechanism for, and the distribution of 5-HT1A receptors.

A

Metergoline/spiperone. Inhibitory increase in K+ conductance. Limbic system, cortex, hypothalamus.

31
Q

Give a preferred antagonist, the mechanism for, and the distribution of 5-HT1D receptors.

A

Ketanserin. Decrease in adenylate cyclase. Cortex, striatum.

32
Q

Give a preferred antagonist, the mechanism for, and the distribution of 5-HT2A receptors.

A

MDL10097, ketanserin. Excitatory decrease in K+ conductance. Cortex (esp. motor), limbic system.

33
Q

Give a preferred antagonist, the mechanism for, and the distribution of 5-HT3 receptors.

A

Ondasetron. Cation channel. Area postrema, limbic system.

34
Q

What are antagonists of the 5-HT3 receptor given to treat?

A

Antiemetics, given to prevent travel sickness and chemotherapy related vomiting.

35
Q

Give some sources of neuropeptides.

A

Neuroendocrine system, plasma derived, vascular endothelium, immune system, growth factors.

36
Q

How does neuropeptide synthesis start?

A

Peptides are first synthesised into a preprohormone that is usually 100-250 amino acids in length and has an N-terminal signal sequence. This is used to indert the preprohomone into the endoplasmic reticulum. Here it is cleaved to form a prohormone.

37
Q

How is peptide diversity achieved?

A

Gene splicing allows for diversity of peptides. This is the inclusion or exclusion of different exons allowing the same gene to encode more than one peptide. Post translational modifications also allows for peptide diversity. Altered modifications may alter peptide function with different proteolytic cleavages generating peptides of different lengths.

38
Q

Describe neuropeptide storage and release.

A

Neuropeptides are stored intravesicularly and are released through calcium dependent exocytosis. They are often found in the same terminals as classical neurotransmitters.

39
Q

How do neuropeptides work?

A

Peptides act as neuromodulators rather than fast neurotransmitters; they are often co-released with other neurotransmitters (co-transmission). The distinction between neuropeptides and hormones is unclear.

40
Q

How are neuropeptides inactivated?

A

Subsequent to release, the activity of the peptides decay by diffusion from site and degradation by peptidases. There is no evidence for re-uptake mechanisms of the peptides.

41
Q

List the reasons why peptides aren’t very good as drugs.

A

Cannot be given orally, expensive to make, often rapidly metabolised, do not cross the BBB.

42
Q

Where are tachykinins found?

A

Substantia nigra, corpus striatum, nociceptive primary afferents, enteric neurones.

43
Q

What are the actions of tachykinins?

A

Contraction of smooth muscle, mixed action of blood vessels, activation of mast cells to release histamine, stimulation of exocrine gland secretions.

44
Q

List the three main families of endogenous opioids.

A

Endorphins, enkephalins, dynorphines.

45
Q

What three distinct genes encode for opioid peptides?

A

Pre-proopiomelanocortin (POMC), Pre-proenkephalin, Pre-prodynorphin.

46
Q

What effects do opioid peptides have?

A

Opioid peptides have both analgesic and cellular inhibitory affects and are released in response to pain.