Serotonin - Receptors Flashcards
What advantage is it for us to have discovered so many serotonin receptors (16)?
Allows us to develop drugs to target each
Where are 5HT-1 receptors found?
Predominantly in the brain where they function as inhibitory presynaptic receptors. Inhibits adenylyl cyclase (decrease cAMP)
Which are the two serotonin auto receptors and where are they located?
On the Soma it is the 5HT-1A
On the terminal it is the 5HT-1D
What does the 5HT-1A receptor do to the neuron?
It opens up the potassium channel so that it hyper- polarizes the neuron
What do the 5HT-1D and 1B receptors do to the neuron?
They prevents the release of the neurotransmitter.
Can you have an inhibitory post synaptic 5HT-1A neuron and if so what does it do?
Yes, it opens a potassium channel and hyper polarizes whatever is at the end of the neuron
What is the second messenger system of 5HT-2?
Phosphatidyl Inosotol triphosphate, which means they increase DAG (activates protein kinase C) and IP3 (releases stored calcium from cells)
What drug is an agonist at the 5HT-1A receptors?
Busipirone (Buspar), and anxiolytic (anti anxiety) agent. It is the only one in the market.
Which drugs are combined 5HT-1B and 1D agonists?
The triptans
What does 5HT stimulation cause in arterial smooth muscle?
Contraction, especially in the carotid circulation.
What is unusual about cerebral blood vessels with respect to serotonin receptors?
Vasoconstriction is mediated by 5HT1 receptors. In most vessels 5HT2 receptors are responsible.
What causes the vasoconstriction which counteracts migrainous vasodilation?
Agonist action at the 5HT-1B receptor.
Are 5HT-1B and 1D receptors auto or hetero receptors?
Both
What does stimulation of 5HT-2 receptors cause?
Constriction of vascular and intestinal smooth muscle. In humans, serotonin is a powerful vasoconstrictor, except in skeletal muscle in the heart, where it dilates vessels and increases microcirculation and vascular permeability.
What does activation of 5HT-2 receptors on endothelial cells cause?
Stimulates the release of nitric oxide in prostaglandins which act locally on smooth muscle cells to cause relaxation.
What does activation of 5HT-2A receptors on platelet membranes cause?
Platelet aggregation
In the CNS, activation of 5HT-2 receptors causes what?
Neuronal excitation in the cerebral cortex
What does activation of 5HT-2B receptors cause?
Stomach fundus contraction
What is the 5HT-3 receptor?
A serotonin gated sodium channel. The binding of serotonin to this receptor opens the channel leading to rapid depolarization of neurons.
Where are 5HT-3 receptors found?
Afferent nerves of baroreceptors and chemo receptors. Also in the coronary bed where they initiate the coronary reflects (inhibit sympathetic outflow) -> profound bradycardia and hypotension (reflex)
- They are found at the vomiting center and the CTZ
What does the stimulation of 5HT-3 receptors in the G.I. tract or brain chemo receptor trigger zone and vomiting center induce?
Nausea and vomiting
What does activation of the 5HT-4 receptor lead to?
An increase in adenylyl cyclase activity and therefore an increase in intracellular cAMP levels
What does activation of the 5HT-4 receptor in the G.I. tract produce?
It produces secretion and facilitates peristalsis
