10

Shahd Mohammed
Lujain Ahmad
Dr. Mohammed Khatatbeh
 (‫)بسم هللا الرحمن الرحيم‬
)‫ كالم الدكتور (ازرق‬. )‫ النوتس (اسود‬+ ‫ كالم الساليدات‬:‫مالحظة‬

MOLECULAR BASIS OF PHYSIOLOGICAL ACTIONS OF THE ANS:

In this lecture we will know: Remember

1. we have 2 neurons forming the
 What types of neurotransmitters are
released ? Synapse:
 What types of receptors these a) Preganglionic
neurotransmitters are bind? b) Postganglionic
Transmitters(‫)النواقل العصبية‬:
2. in sympathetic we have:
 At ganglion: preganglionic neurons a) short preganglionic
of both sympathetic and b) long postganglionic
parasympathetic release 3. in parasympathetic we have:
acetylcholine (Ach).
a) long preganglionic

b) short postganglionic

Sympathetic paraSympathetic Now, as neurotransmittters released by

these neurons.
 At effector organs:
- Post ganglionic terminals of
parasympathetic fibers release
acetylcholine

Sympathetic

The first neuron (preganglionic) of both

sympathetic and parasympathetic they are
paraSympathetic
releasing acetylcholine(Ach)
- Post ganglionic terminals of
sympathetic fibers release
norepinephrine. An exception for
sympathetic nerves to sweat glands,
which release acetylcholine (Ach). parasympathetic

The second neuron of parasympathetic

they are also releasing acetylcholine, but
Sympathetic
The second neuron of sympathetic they are
releasing norepinephrine(NE)
 In addition, we have an exception with
regard to the second neuron (the
postganglion neuron) which are innervation
to sweat gland and fibers of smooth muscle
Sympathetic They are releasing acetylecoline(Ach)

Now, What about the somatic fibers, the motor neuron as we see down:

Q) What type of neurotransmitter they are releasing?

 The released acetylcholine(Ach) by
- Acetylecholine (Ach) also parasympathetic system is
inactivated by breakdown by
acetylcholinesterase.

 Epinephrine(EP) is inactivated by
recapture)‫ (استعادة‬by postganglionic
nerve varicosities.

Also here including

What’s happen at

the Adrenal gland

(the suprarenal gland)

Note that: the adrenal gland

is classified as sympathetic.
this table shows what’s happening..

We have 2 On the 2nd neuron This receptor gates ligand gated Na+
receptors channel. Activation of this receptor will
On the effector cell
cause depolarization on postsynaptic
Receptor at ganglion(2nd neuron): membrane.
Nicotinic receptors:
Simply Ach binding to nicotine receptor
On post synaptic membrane of sympathetic causing the activation of Na+ channels
and parasympathetic there are nicotinic (remember the purpose is to generate the
receptors. “These receptors are excited by action potential)
acetylcholine( C7NH16O2+ )”
Nicotinic Q) why we call this receptor “nicotinic”?
receptor
- because The drug nicotine (C10H14N2) can
also stimulate these receptors.
This receptor is similar but not identical
(they have different subunit structures) to
nicotinic receptor of the neuromuscular
junction.
Receptors on effector cells:
‫ ؟‬cholinergic‫ليش امسهم‬
1- Muscarinic receptors:
From the name Ach
These cholinergic receptors lie on effector
cells of parasympathetic neuro-effector
junctions. Muscarinic
receptor
Q) why we call this receptor “muscarinic”?
- because the drug muscarine can stimulate
these receptors.
Q) what is the muscarine?
- it is an active substance which can be
found in toxic mushroom( ‫)فطر سام‬
 They differ from nicotinic receptors
found on ganglia and neuromuscular
junction.
 Many muscarinic receptors have been
known (M1-M5) at these junctions. All
these receptors are coupled to G
protein.
1) Inhibitory:
- The inhibitory receptor that is found in the
heart (M2) is coupled via G protein to
Activation of K+ channels this receptor will
slow the rate of depolarization. And that’s
found in Conductive tissue of heart,
Remember.. What is the property of
conductive tissue? They generate
automatically the Action potential

Muscarinic Receptors
(M1-M5)
Inhibitory Excitatory
1) M2 in the heart (M1,M3,M5)
The rate of depolarization becoming slower
G protein Found on:
so you’re needing longer time between two
K+ channel 1) smooth muscle action potential to develop.
Slow rate of 2) glands So the number of action potential
depolarization decreasing which is resulting in Slowing of
Gq protein
2) other: the heart rate (Bradycardia).
Phospholipase C
Gi - Other inhibitory muscarinic receptors are
“this enzyme negatively coupled via Gi protein to adenylyl
Adenylyl Cyclase
increases cyclase and decrease production of c-AMP.
Reduce cAMP production of The reduction of c-AMP can inhibit the ca+
3) M4 (doctor said inositol-1,4,5- channels and Na+ channels also.
“I think” ) triphosphate(IP3)"
2) Excitatory:
- The excitatory receptors (M1, M3, M5)
- found on smooth muscle (eg.
Gastrointestinal tract) and glands
- They are coupled via Gq protein to
phospholipase C. (This enzyme increases
production of inositol-1,4,5-trisphosphate
(IP3).
-IP3 causes release of Ca++ from internal
stores in muscle or glands, causing
contraction or secretion.
These receptors are activated by muscarine and
inhibited by atropine.
Muscarine poising(Toxification):
The targets of muscarinic receptors’ stimulation are
illustrated by muscarine poisoning. These effects
include: (what’s happen if someone has ingested the
toxic mushroom?) PARASYMPATHETIC symptoms
1) stimulation of secretory activity: salivation,
tearing, sweating, nasal and bronchial
secretion.
2) Increase gastrointestinal tract motility
3) vomiting and diarrhea.
4) Contraction of urinary bladder (urination).
5) Slowing of the heart (Bradycardia).
6) constriction of pupil
Now to treat the patients with these effects
we need to block the Muscarinic Receptor
and the drug that is useful is Atropine 
Actually you mainly need 10-15 injections of
Atropine to start reverse the effect + you
have to watch some sites (heart rate,
pupil,…)
So as we said, Muscarinic receptors are
blocked by atropine from a plant “atropa
belladonna” which induces reversal effects
of muscarinic poisoning.
If you give higher amount of atropine, what
will happen?
Effects of atropine include:
1) Inhibition of glandular secretions. dry
mouth, dry eyes, and dry nasal passages.
2) Tachycardia. (increase heart rate).
3) Loss of pupillary light reflex.
As you now anyone if you projecting light on
your eye, your pupil will constrict(‫)تنقبض‬,
because the activation of parasympathetic.
Now if you are given Atropine, that reflex is
lost so they are not getting constriction.
4) Loss of ability to focus the lens for near
vision.)‫)فقدان القدرة عىل رؤية الاش ياء القريبة‬
At pharmagist: they are using atropine drops to get
dilation of pupil (mydriasis) and to enable
pharmagist projecting light to examine the
fundus(‫ )معق‬of the eye. Once they are projection,
these persons are loosing the focus for the near
vision. And the The doctor is asking you for 4-5
hours don’t read, because you’ve lost the control for
the lens.
2-Adrenergic receptors: (we can have both
 Stimulation of this receptor produces
neurotransmitter and hormone binding to them)
excitation. This effect involves IP3
These receptors respond to production and release of Ca++ from
catecholamines (epinephrine (Epi) and intracellular stores. Some (α1 are
norepinephrine (NE)). (Remember NE and coupled to Ca++ gated channels).
EPI also released from suprarenal gland, so
both molecules acting over the same types
of receptors (adrenergic), but we can add
differences in the affinities for binding. We
have many subtypes of adrenergic
receptor.)

Two types of receptors are known alpha

(α) and beta (β) receptors. ‫الصورة من خارج الساليدات‬

 Alpha2 receptors: are found on

β α sympathetic postganglionic nerve
terminals.
β2 β1 (inhibitory) α2 α(Excitatory)
1  These receptors are important for self
(inhibitory) (Excitatory) inhibition of NE release.
‫انبساطية‬ Self inhibition ‫انقباضية‬
In heart
Effector cell ‫الطبيعي انه المستقبل يكون على‬
Alpha receptors:
postganglionic ‫ولكن يوجد مستقبل اخر على‬
The alpha receptors are subdivided into α1 ‫كتير يرتبط على المستقبل‬ NE ‫عشان لما يفرز‬
and α2 receptors. Remember: we have some
NE‫اللي عليه ويحفزه يقلل‬
vessels responding by vasoconstriction like fight or (Negative Feedback)
flight reaction ,the vessels of the skin and arterior These receptors are found
they are responding vasoconstriction, but vessels over adrenergic neurons
which are supply muscles you’re getting (neurons which are releasing
vasodilation both of them they are innervated by NA and EPI)
the sympathetic but, in certain structure we’re  Similar receptors are found on
getting excitation in other structure we’re getting
nonadrenergic terminals are called
relaxation of these smooth muscle cells , we have
Alpha2 heteroreceptors.
these differences because we have differences in
(also they inhibiting these nonadrenerginc
the types of receptors they are binding.
neurons)
The alpha 1 (α1) receptor is widely  These receptors are negatively
distributed on smooth muscles (eg. In coupled to adenylyl cyclase via Gi
vessels and arterios) with the exception of protein and decrease c-AMP
bronchial muscle. NE and EPI are about production.
equally effective on these receptors.
Q) imagine if somebody is playing football and getting
injury, is he feeling pain during the activity? No,
The β2 receptors are preferentially
Because the pathways which are transmitting these activated by EPI rather than NE.
sensations, it has some adrenergic neurons (which are
releasing NE) at the same time the postganglionic
neuron in that pathway we have some neurons bearing
α2 heteroreceptors which inhibiting the high release of
Patients who have higher heart
NE and epi. ‫ وببلش يشعر باأللم‬NE,EPI‫لما يرتاح الشخص بقل افراز‬ rate 
Beta receptors: They are given β blockers
These receptors are subdivided into beta1
(β1) and beta 2 (β2) receptors.
1) Decreasing the heart rate
- Both of them are more sensitive to
catecholamines than alpha receptors “because you’re reducing the activity
(catecholamines stimulate these receptors at or effects of sympathetic over this
much lower concentration than stimulation structure”
of alpha receptors).
2) constriction the bronchial
 Beta 1 (β1) receptors: found on heart muscle “because you haven’t the β2”
and produces excitation in the heart.
It’s found over the conductive tissue of • All subclasses of adrenergic receptors
the heart muscle. Heart muscle will can be blocked by specific blocking
increase the contraction+ conductive agents (antagonists).
tissue will generate more action
• β1 blockers are useful as antiarythmic
potential. (because of that we
considere it us excitatory receptor) drugs. (‫)مضاد اضطراب النظم‬
 Beta 2 (β2) receptors: found on •β2 selective agonist (produce
tracheal and bronchial smooth muscle, activation of β2 receptor) will dilate
in the gastrointestinal tract, and on
bronchi. This agonist is useful in
smooth muscles of blood vessels
asthma(‫)الربو‬. During Asthma:
supplying skeletal muscles (occurs
along with alpha 1 receptors). 1- constriction of
1- Vasodilation ( ‫ (توسع االوعية‬because
the smooth muscles of these vessels
Bronchioles
are having more β2 receptors. 2- high secretion
2- Bronchodilation( ‫)توسع القصبات‬ in the airways
because of the relaxation of smooth
muscles there. pateint with Asthma cann’t take β2
3- decrease the activity of blocker, but Nowadays they take β1
gastronintestinal tract blocker..
In this case if a patient has higher heart
This will result in subsequent
rate and Asthma, you can give the β1
blockers to reduce the activity of
activation of protein kinase and
sympathetic over the β1 phosphorylation of one or more
proteins.
Also you can give EPI to these patient
as drug to get Brochodilation, BUT you The response elicited depends on
have to be carefull with regard to the the role of phosphorylated
heart rate not to have increasing the proteins.
rate to 100 and die! ( it is actually given
to children sometimes)

The MECHANISM:
Both receptors are positively coupled
to adenylyl cyclase via Gs protein, and
increase c-AMP. (we can have different
effects over different structures)

To some up! the types of receptors:

For example here:
The Increasing c-AMP can activate Na+
channels and Ca++ channels
The activation of Na+ channels will
make the rate of depolarization faster
so we’ll have higher heart rate
Also, in smooth muscle the Inhibition
of Ca++ channels will cause relaxation
of smooth muscle cells.
1. On ganglia
Sympathetic and parasympathetic have
nicotinic receptors at the post synaptic
membrane
2. On effector cells
a) Muscarinic receptors for Ach in
parasympathetic (and sometimes
on sympathetic as will)
b) Adrenergic receptors for NE and EPI
 Past Papers 😍
Q1) All the following structures are bearing muscarinic receptors EXCEPT:
a) Postganglionic neurons b) sweet gland c) intestine
d) salivary glands e) heart conductive tissue

Q2) by muscarinic intoxication, all the followings are taking place EXCEPT:
a) vomiting and diarrhea b) dilation of pupil( mydriasis)
c) hypersalivation d) Increased intestinal motility
e) Excessive sweating f) decrease heart rate

Answers:
Q1) A
Explanation: Although the postganglionic neurons receive Ach, they have
nicotinic not muscarinic receptors
Q2) B
Explanation: Muscarinic toxicity means the ingestion of high amounts of
muscarine (mushroom)
Symptoms of this toxication is simply the symptoms of PSNS over-activation
with excessive sweating (as the sweat glands have muscarinic receptors).

..💖‫ابلتوفيق‬
" ‫"س بحانك اللهم وحبمدك أشهد أن ال اهل الا انت أس تغفرك وأتوب اليك‬