Test 2: lecture 23 serotonin Flashcards
where can you find 5-HT
serotonin
- 90% in the enterochromaffin cells of GI tract
- platelets (not made there, but carried there)
- 1-2% in CNS as NT
- mast cells of rodents and cattle
compare EC an ECL cells
what do they make
where are they found
what is their role
EC:
* serotonin
* small intestine, colon and appendix
* intestinal motility and secretion
ECL:
* histamine
* stomach wall
* acts on parietal cells to increase gastric acid release
rate limiting step of serotonin release
tryptophan 5 hydroxylase
serotonin in the — can turn into melatonin
pineal gland
— will breakdown serotonin into products that can be excreted in the urine
monoamine oxidase (MAO-A)
turn over estimated by ratio of 5HIAA:5-HT
how is serotonin made in the brain
tryptophan is actively transported into brain where tryptophan hydroxylase 2 turns it into serotonin
serotonin is then packaged into vesicles for transport and release
most serotinin receptors are —, except for — which is a — receptor
GPCR
5-HT3= ligand regulated channel →emetic response
— serotinin receptor will inhibit cAMP
5-HT1
— serotonin receptor will increase IP3 in smooth muscle
5-HT2
GPCR
what will an autoreceptor do
negative feedback
will stop further release of that substance
5-HT1D/1B are autoreceptors at the presynaptic terminal
5-HT1A is a somatodenritic autoreceptor
effect of serotonin on cardiovascular system
- Contraction of vascular smooth muscle, especially splanchnic, renal pulmonary and cerebral vasculatures. (mainly 5-HT 2 receptor)
- Positive ionotropic and chronotropic effects on heart. (stronger contraction = ↑CO)
serototin will do what to platelets
- Mechanisms for uptake, storage & endocytosis of 5-HT.
- increases adhesion, aggregation, and thrombus formation to plug holes in endothelial wall of vasculature. Can also cause vasoconstriction to promote hemostasis. (5-HT2A)
what does serotonin do in GI tract
food pressing(mechanical stimulation) on EC cells causes release of serotonin
serotonin will affect the enteric nervous system and affect peristalsis and acid secretion
Serotonin overproduction in carcinoid tumor will do what to GI tract
cause severe diarrhea
serotonin will lead to formation of melatonin in the pineal gland, which controls
hormone, biological clock and circadian rhythm, sleep regulation
— in the brainstem make serotonin
raphe nuclei
effects of serotonin on CNS
a) Sensory perception, including pain
b) Sleep
c) Autonomic and endocrine function
d) Mood, aggression, sexuality
e) Appetite
f) Cognition
g) Emesis (bad food, EC cells release 5-HT, high 5-HT levels bind to 5HT3 receptors and cause emesis) (in humans and dogs)
how to alter endogenous 5-HT levels
↑ tryptophan- in therory, but not actually effective
inhibit 5-HT synthesis- usually toxic
block serotonin reuptake
MAO inhibitors
what are some serotonin uptake blockers
- Tricyclic “antidepressants” (TCAs)
- SSRI (selective serotonin reuptake inhibitors)
- MDMA “ecstasy” prevents reuptake and induces high 5-HT secretion: postsynaptic flooding effect.
increases serotonin effect by prolonging its time in the synaptic cleft
how does MAO inhibitors effect serotonin
MAO is found inside nerurons and breaks down serotonin.
if you stop this serotonin can be repackaged and released
— inhibit reuptake of serotonin on the presynaptic cell, partially inhibit
— reuptake as well by blockade of amine pump
Tricyclic antidepressants (TCAs)
norepinephrine
Amitryptiline HCl (Elavil®)
Clomipramine HCl (Clomicalm®)
Imipramine HCl (Tofranil®)
stop reuptake of NE and serotonin
what are some TCA drugs
Amitryptiline HCl (Elavil®)- anxiety, neuropathic pain, feather plucking
Clomipramine HCl (Clomicalm®)- OCD- urine marking, mounting
Imipramine HCl (Tofranil®)- separation anxiety, urinary incontinence, ED
act to inhibitor serotonin and NE reuptake
what are some SSRI
Fluoxetine HCl (Prozac®, Reconcile® for dogs: anxiety, destructive behaviors, inapporopriate elimiation
Paroxetine HCl (Paxil®)
Sertraline (Zoloft®)
—, H1 receptor antihistamine allergy medication is also SNRI
Chlorpheniramine (diathal)
stops reuptake of NE
what are some MAOA inhibitors
Irreversible (Clorgyline®)
reversible inhibition (RIMA)
inhibit serotonin/norepinephrine degradation
what are some MAO B inhibitors
Anipryl®
stop dopamine >serotonin degradation
what happens with ergot toxicity
acts as serotonin receptor agonist
made from a fungus
in animals can cause: pain, erratic behavior, staggering, convulsions, abortion, gangrene and loss of limbs
Dolasetron Mesylate
5-HT3 antagonist
antiemetic
especially in chemotherapy
Ondansetron
5-HT3 antagonist
potent antiemetic
limited use in severe nausea/vomiting, Zofran®,
available as an inhaler?
psilocybin acts as a — agonist
5HT1A
5HT2A/AC
serotonin syndrome
toxic levels of serotonin
that can cause restlessness, tachycardia, diarrhea. Can be lethal.
can treat with benzodiazepines (diazepam) which is a 5HT antagnoist that will cause depression of CNS activity?
