Neurotransmitters Flashcards
What proportion of prescriptions are made up of CNS active drugs?
1 in 6.
Outline the synthesis of noradrenaline from tyrosine.
Tytrosine, (tyrosine hydroxylase) L-Dopa, (L-aromatic amino acid decarboxylase) Dopamine, (dopamine beta hydroxylase) Noradrenaline.
Which step of the synthesis of noradrenaline is the rate limiting step?
The first step.
What is L-DOPA used to treat? How does it work?
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.
What is noradrenaline stored in?
Dense cored vesicles 70-200nm in diameter.
How does Reserpine modulate noradrenaline action?
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).
Define quanta.
Quanta is defined as the amount of neurotransmitter released in one vesicle.
Outline the release of noradrenaline.
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.
Describe both of the two uptake mechanisms used in noradrenaline inactivation.
There are two uptakes; uptake one involves reuptake into neurones and uptake two involves reuptake into non-neuronal elements such as glial cells.
Give the characteristics of noradrenaline uptake 1.
Low capacity, high affinity. 75% uptake. Takes up other substrates suych as dopamine and 5-HT (serotonin). Inhibited by cocaine, amphetamine, and tricyclic antidepressants.
Give the characteristics of noradrenaline uptake 2.
High capacity, low affinity. 25% reuptake. Inhibitd by normetanephrine and steroid hormones.
Give a preferred agonist, perferred antagonist, and the mechanism for alpha 1 adrenoreceptors.
Phenylephrine. Prazosin. K+ conductance.
Give a preferred agonist, perferred antagonist, and the mechanism for alpha 2 adrenoreceptors.
Clonidine. Yohimbine. Ca2+ conductance.
Give a preferred agonist, perferred antagonist, and the mechanism for beta 1 adrenoreceptors.
Isoproterenol & Dobutamine. Metoprolol. K+ conductance.
Give a preferred agonist, perferred antagonist, and the mechanism for beta 2 adrenoreceptors.
Salbutamol. Butoxamine. NO pathway.
How does the action of alpha 1 adrenoreceptors, K+ conductance, have an effect.
Potassium is blocked from leaving the cell, preventing hyperpolarisation, leading to net excitation.
How does the action of alpha 2 adrenoreceptors, reducing calcium conductance, have an effect.
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.
Define an autoreceptor and give an example.
Autoreceptors are where the receptor recognises the transmitter that is released from that terminal. E.g. alpha 2 adrenoreceptors.