question on serotonin

[Hokie06]

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I'm a little confused on the effects of serotonin and was wondering if some one could shed some light.

with carcinoid syndrome you find --> flushing, diarrhea, along with other things.

my question is this.

sumatriptan is a serotonin agonist and is used to treat cluster and migraine headache via vasoconstriction. so why is it that serotonin acts as an vasoconstrictor here and then work as a vasodilator in the face?

also, odansetron is a serotonin antagonist and its toxicity is headache and constipation. constipation makes sense but again antagonizing serotonin receptors seem to vasodilate vessels to the head?

any clarification would be greatly appreciated! thanks! 🙂

 

[whoknows2012]

I'm a little confused on the effects of serotonin and was wondering if some one could shed some light.

with carcinoid syndrome you find --> flushing, diarrhea, along with other things.

my question is this.

sumatriptan is a serotonin agonist and is used to treat cluster and migraine headache via vasoconstriction. so why is it that serotonin acts as an vasoconstrictor here and then work as a vasodilator in the face?

also, odansetron is a serotonin antagonist and its toxicity is headache and constipation. constipation makes sense but again antagonizing serotonin receptors seem to vasodilate vessels to the head?

any clarification would be greatly appreciated! thanks! 🙂

I can at least answer part of the question...the flushing in carcinoid syndrome is not from serotonin itself, but from increased secretion of kallikrein leading to vastly increased levels of bradykinin=potent VD.

The ondansetron vs sumatriptan example most likely lies in the type of receptors being agonized/antagonized, as odansetron is a 5HT3 antagonist while triptans are 5HT1b/d agonists. Hope this helps

 

[coralis]

Your response is in the receptors. Remember serotonin has a wide range of activity as well as a wide range of receptors, some of these act differently than their cousins.
so we have the following:

5HT1 via Gi, in the CNS and affects behaviour and does vasonconstriction. Migraines are actually due to too much vasodilation, the initial vasoconstriction will give you the aura to a migraine, but the PAIN is due to the DILATION --> thus Sumatripan as a specific 5HT1D agonist will cause vasoconstriction.

5HT2 via Gq... don't really know of a pharm use of this one, but involved in Platelet aggregation, smooth muscle contraction, consider what Gq affects... that is IP3/Dag --> Ca

5HT3 is actually an ion channel and NOT Gprotein linked like all the others, and it's found in the area postrema, hence Ondansetron as an atagonist will block it's action and thus subside emesis

5HT4 acts via Gs and it is mostly found in the gut.

Now, although these are receptor specific we know that they might still act on other serotonin receptors. Since we're giving someone ondansetron for emesis and not headaches it means they're vasculature was in the brain was normal now we're dilating it --> which is the same thing like migraine, where vasodilation will cause a shift in pressure and thus some leakage in the brain picked up by pain receptors. In summary you treat a migraine with vasoconstriction and you induce one with vasodilation.

As for the carcinoid syndrome.... I guess my answer would be we have poop loads of serotonin and they're activating receptors here and there and the body is trying to react against this.

Hope this helps