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Notes:
Dopa: Dihydroxyphenyl alanine.
Types of catecholamine: Dopamine, Norepinephrine and
Epinephrine.
Dopamine doesn't contain a hydroxyl group on C (take a look at the
figure).
Norepinephrine contains a hydroxyl group on C. This hydroxyl group
(which is found in norepinephrine but not in dopamine) makes many
differences between norepinephrine and dopamine: different
receptors, actions and locations.
If we methylate the amine group in norepinephrine (nor methyl) we
will have epinephrine. This methyl group makes the Epinephrine
more selective to the β-receptors than norepinephrine. (More bulk
Æmore selective for β-receptors).
Catecholamine:
Structure: catechol + amine
Catechol: benzene ring with 2 hydroxyl groups in Ortho and
Meta positions. We call this structure in organic chemistry
chatecol nucleus.
Inhibited by 2 enzymes:
1-MAO (monoamine oxidase): it links to catecholamine by
o- monoamine oxidase. It is a mitochondrial enzyme in the liver
and nervous tissue. It oxidizes the amine group and the carbon
next to it.
2-COMT (catechol-o-methyltransferase): -conjugate to
catecholamine mainly in the liver and other tissues.
Notes:
It doesn’t matter which one (MAO, COMT) acts first we will have
the same end result.
whatever the enzymes acts first or if you are talking about
epinephrine or norepinephrine, the final product is Vanil Mandelic
Acid (VMA or 3-methoxy-4-hydroxy-mandelic acid)
VMA: if we have excessive sympathetic stimulation and we expect
that the concentration of epinephrine or norepinephrine is high
(hard to measure) and we found that VMA is highÆ we know that
the concentration of epinephrine, norepinephrine or both of them
is high.
Tumors in sympathetic chain (ex: phyochromocytoma) secretes
tremendous amounts of catecholamine.
If the patient comes to your clinic and told you that he is suffering
from rapid hypertension for a short while then his pressure returns to
the normal. You realize that the problem is: phyochromocytoma.
The same problem happens also in some patients in fear, fight and
flight Æ suddenly increasing in the hypertensionÆblood pressure id
high (presence of catecholamine). So you –as a DR- ask him to bring a
urine sample, and then check the VMA concentration.
Dopamine:
-metabolized by MAO and COMT also
-The end product is Homovanillic acid
-if there is an increase of the homovallinic acid in the urine, this
leads to an increase concentration of dopamine.
Autonomic Receptors:
**D1 receptors:
• Found mainly in the brain.
• Present in renal vascular bed.
• Responsible for vasodilation in renal blood vessels to protect
the kidney from ischemia (kidney weight= 5/1000 of total
body weight, but it receives 25/100 of the cardiac output) if
there is ischemia in the kidney and D1 receptors are
deactivated, kidney will go under necrosis. So D1 receptors
are protective system for the kidney.
Presynaptic Regulation:
- B-adrenoceptors are B1
- If the Norepinephrine is low in the body, B1 receptors will be
stimulated.
- If the Norepinephrine is high in the body, a2 receptors will be
stimulated.
Postsynaptic Regulation:
-Up-regulation: synthesis
-Down regulation: blocking of the receptors
-If you have excessive stimulation of Alpha receptors Æ down regulation
occurs to achieve the balance.
-When there is blocking of Alpha receptors Æ Up-regulation occurs to
achieve the balance.
-Down regulation and Up-regulation happen in seconds to days.
-In seconds: endocytosis (down regulation because of excessive
stimulation)
-In days: when there is protein synthesis (stimulation or inhibition)
*You have to memorize these actions.
In The Eye:
: Myoses: constriction of pupil.
: Medriosis: dilation of pupil.
: Iris has 2 muscles: circular and radial
:
: If the circular muscle is stimulated Æ constriction (myoses)
: If the radial muscle is stimulatedÆ dilation (medriosis)
: Ciliary muscle is stimulated by B-adrenergic receptors and M3
cholinergic receptors.
-M3 receptors contract the ciliary muscle to accommodate for near
vision. (Accommodate: focus and adapt your eye for near vision)
- B-receptors relax the ciliary muscle of eye for far vision.
In The Heart:
S.A node: pacemaker.
We have B1 and B2 sympathetic receptors. B1 are more in No. than
B2.
B1 are also more important than B2. Æ Acceleration to the heart
and any ectopic pace maker. They also increase the contractility of
the heart
Parasympathetic activity receptors (M2 receptors) Æ decelerate
the heart. M2 receptors also decrease the contractility of the
heart especially in the atrium.
In blood vessels:
-What is the M3 sympathetic receptor??!!!
Answer: certain neurons in sympathetic nervous system use acetylcholine.
These neurons are called sympathetic cholinergic receptors. We have this
type of receptors in: 1-sweat glands 2-some blood vessels.
-Cholinergic system (M3, M5) relax smooth muscles of certain blood
vessels indirectly. The receptors stimulate the endothelium to secrete
EDRF (endothelium derived relaxing factor) which will relax the smooth
blood vessels. (Two steps: 1- cholinergic receptors in endothelial cells
secrete EDRF. 2- EDRF inhibit (relax) the smooth muscles in blood
vessels)
-EDRF: nitric oxide.
Best Wishes
KhaleD HajjiR