Test 2: lecture 23 serotonin

Question 1

where can you find 5-HT

Answer 1

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

Question 2

compare EC an ECL cells
what do they make
where are they found
what is their role

Answer 2

EC:
* serotonin
* small intestine, colon and appendix
* intestinal motility and secretion

ECL:
* histamine
* stomach wall
* acts on parietal cells to increase gastric acid release

Question 3

rate limiting step of serotonin release

Answer 3

tryptophan 5 hydroxylase

Question 4

serotonin in the — can turn into melatonin

Answer 4

pineal gland

Question 5

— will breakdown serotonin into products that can be excreted in the urine

Answer 5

monoamine oxidase (MAO-A)

turn over estimated by ratio of 5HIAA:5-HT

Question 6

how is serotonin made in the brain

Answer 6

tryptophan is actively transported into brain where tryptophan hydroxylase 2 turns it into serotonin

serotonin is then packaged into vesicles for transport and release

Question 7

most serotinin receptors are —, except for — which is a — receptor

Answer 7

GPCR

5-HT3= ligand regulated channel →emetic response

Question 8

— serotinin receptor will inhibit cAMP

Answer 8

5-HT1

Question 9

— serotonin receptor will increase IP3 in smooth muscle

Answer 9

5-HT2

GPCR

Question 10

what will an autoreceptor do

Answer 10

negative feedback

will stop further release of that substance

5-HT1D/1B are autoreceptors at the presynaptic terminal

5-HT1A is a somatodenritic autoreceptor

Question 11

Answer 11

Question 12

effect of serotonin on cardiovascular system

Answer 12

• 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)

Question 13

serototin will do what to platelets

Answer 13

• 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)

Question 14

what does serotonin do in GI tract

Answer 14

food pressing(mechanical stimulation) on EC cells causes release of serotonin

serotonin will affect the enteric nervous system and affect peristalsis and acid secretion

Question 15

Serotonin overproduction in carcinoid tumor will do what to GI tract

Answer 15

cause severe diarrhea

Question 16

serotonin will lead to formation of melatonin in the pineal gland, which controls

Answer 16

hormone, biological clock and circadian rhythm, sleep regulation

Question 17

— in the brainstem make serotonin

Answer 17

raphe nuclei

Question 18

effects of serotonin on CNS

Answer 18

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)

Question 19

how to alter endogenous 5-HT levels

Answer 19

↑ tryptophan- in therory, but not actually effective

inhibit 5-HT synthesis- usually toxic

block serotonin reuptake

MAO inhibitors

Question 20

what are some serotonin uptake blockers

Answer 20

• 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

Question 21

how does MAO inhibitors effect serotonin

Answer 21

MAO is found inside nerurons and breaks down serotonin.

if you stop this serotonin can be repackaged and released

Question 22

— inhibit reuptake of serotonin on the presynaptic cell, partially inhibit
— reuptake as well by blockade of amine pump

Answer 22

Tricyclic antidepressants (TCAs)

norepinephrine

Amitryptiline HCl (Elavil®)
Clomipramine HCl (Clomicalm®)
Imipramine HCl (Tofranil®)

stop reuptake of NE and serotonin

Question 23

what are some TCA drugs

Answer 23

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

Question 24

what are some SSRI

Answer 24

Fluoxetine HCl (Prozac®, Reconcile® for dogs: anxiety, destructive behaviors, inapporopriate elimiation

Paroxetine HCl (Paxil®)

Sertraline (Zoloft®)

Question 25

—, H1 receptor antihistamine allergy medication is also SNRI

Answer 25

Chlorpheniramine (diathal)

stops reuptake of NE

Question 26

what are some MAOA inhibitors

Answer 26

Irreversible (Clorgyline®)
reversible inhibition (RIMA)

inhibit serotonin/norepinephrine degradation

Question 27

what are some MAO B inhibitors

Answer 27

Anipryl®

stop dopamine >serotonin degradation

Question 28

what happens with ergot toxicity

Answer 28

acts as serotonin receptor agonist

made from a fungus

in animals can cause: pain, erratic behavior, staggering, convulsions, abortion, gangrene and loss of limbs

Question 29

Dolasetron Mesylate

Answer 29

5-HT3 antagonist
antiemetic
especially in chemotherapy

Question 30

Ondansetron

Answer 30

5-HT3 antagonist
potent antiemetic
limited use in severe nausea/vomiting, Zofran®,
available as an inhaler?

Question 31

psilocybin acts as a — agonist

Answer 31

5HT1A
5HT2A/AC

Question 32

serotonin syndrome

Answer 32

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?