Autonomic nervous system

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Books/Autonomic nervous
system/Introduction
From Pharmpedia
Autonomic Nervous System
1. Introduction
2. Sympathetic system
3. Parasympathetic system
4. Enteric nervous system
5. Neurotransmission
6. Receptors
7. Cholinergic receptors
8. Adrenergic receptors

9. Physiology
Nervous system plays an important role in the control and coordination of biological function
at sub cellular, cellular and at higher levels for the regular activity as well as for the
correction of abnormal activity. The nervous system receive stimuli transmits the
information at higher centre and initiate response that help in the well being of the
organism.
Nervous system is divided into two parts

• central nervous system and

• peripheral nervous system

peripheral system is further divided into

autonomic nervous system (ANS) and somatic nervous system.
This ANS is again divided into
parasympathetic nervous system and
sympathetic nervous system.
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Autonomic Nervous System

The organs (the "viscera") of our body, such as the heart, stomach and intestines, are
regulated by a part of the nervous system called the autonomic nervous system (ANS). The
ANS is part of the peripheral nervous system and it controls many organs and muscles
within the body. In most situations, we are unaware of the workings of the ANS because it
functions in an involuntary, reflexive manner. For example, we do not notice when blood
vessels change size or when our heart beats faster. However, some people can be trained to
control some functions of the ANS such as heart rate or blood pressure.
The ANS is most important in two situations:
1.In emergencies that cause stress and require us to "fight” or take "flight" (run away and )
2.In non emergencies that allow us to "rest" and "digest."

Autonomic is a combination of two words autos (self) and nomos (regulating). Thus ANS
has a property to regulate organ functioning automatically. Thus it could maintain the
homeostasis of an organ to exist. The two subparts of ANS, parasympathetic nervous
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system participates in conserving the energy while sympathetic nervous system participated
in utilizing the energy.
If any system innervates only by parasympathetic or sympathetic system then their effect is
controlled by their own mechanism or by some third system while, if both are innervating to
same system then their activity is controlled by the activity of other system.
The above can explained by the following example Heart an organ innervates by both
parasympathetic and sympathetic nervous system so if sympathetic system gets activated
means energy is utilized in the form of heart contraction or increased heart beat so to relax
the myocardial muscle parasympathetic system gets activated and relax the myocardial
muscle as the demand for oxygen by the body is decreased but do remember that in normal
condition they are in the state of dynamic equilibrium i.e. myocardial muscle have specific
rate of muscle contraction and muscle relaxation for normal demand biological system.
Now again a question arises in the mind that why this dynamic equilibrium is shifted to one
side the answer is, supposing you are doing vigorous exercise means you are utilizing
energy i.e. Your sympathetic system is in activated stage and why after 10 or 15 minutes
your breath becomes normal, because parasympathetic system starts superseding the
sympathetic system to conserve the energy beyond the needed amount.

The ANS regulates:

Muscles

• In the skin (around hair follicles; smooth muscle)

• Around blood vessels (smooth muscle)

• In the eye (the iris; smooth muscle)

• In the stomach, intestines and bladder (smooth muscle)

• Of the heart (cardiac muscle)

Glands
The ANS is divided into three parts:

• The sympathetic nervous system

• The parasympathetic nervous system

• The enteric nervous system

Books/Autonomic nervous
system/Sympathetic system
From Pharmpedia
The preganglionic neurons of the sympathetic nervous system have their origin (cell bodies)
in the thoracic and lumbar region (thoracolumabar) of the spinal cord. There are two major
groups of sympathetic ganglia, Para vertebral ganglia (lie in vertebral column) and
prevertebrl column (lie in abdomen; e.g. celiac or mesenteric ganglia). The adrenal medulla
resembles a sympathetic ganglia and preganglionic fibres innervate it.
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Sympathetic nervous system

Books/Autonomic nervous
system/Parasympathetic system
From Pharmpedia
The preganglionic axons of the parasympathetic system have their origin (cell bodies) in the
lower brain (cranium, i.e. mid brain and medulla oblongata) and in the sacral portion of the
spinal cord (craniosacral region) the parasympathetic ganglia are located usually very close
to or in the effecter organ. The parasympathetic fibres are long while the postganglionic
axons arising from parasympathetic ganglia are short.
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Books/Autonomic nervous system/Enteric

nervous system
From Pharmpedia
The enteric nervous system is a third division of the autonomic nervous system that you do
not hear much about. The enteric nervous system is a meshwork of nerve fibers that
innervate the viscera (gastrointestinal tract, pancreas, and gall bladder).
Scientists who study the network of nerves surrounding the esophagus, stomach and
intestines compare it to a microcomputer, and call the better-known brain-in-the-head a
"mainframe." But while microcomputers represent the future of silicon processing, this
biological micro-in-the-belly is a relic of the distant past, of a time when the most important
thing in life was eating.
The enteric nervous system, present in all vertebrates has these functions: to regulate the
normal (digestive) activity of the digestive system and prepare it for whatever its future
may hold: whether it be sampling lobster thermidor or dodging a headlong charge from the
king of the tigers.
With a population of 100 million nerves, the enteric nervous system is as complex as the
better studied spinal cord. And like the spinal cord, it transmits and processes messages.
(Want to see our coverage of spinal cord repair? Things could be looking up for paralyzed
people.)
And while a skull doesn’t protect this nervous system, many of its structures and chemicals
parallel those of the mainframe brain. It has sensory and motor neurons, information
processing circuits, and the glial cells. It uses the major neurotransmitters: dopamine,
serotonin, acetylcholine, nitric oxide and norepinephrine. It even has benzodaizepines,
chemicals of the family of psychoactive drugs that includes Valium and Xanax.

Books/Autonomic nervous
system/Neurotransmission
 6
From Pharmpedia
A nerve consists of lots of neurons and all these neurons are connected with each other with
synaptic cleft (space between head of one neuron and tail of another neuron), this called
synapse and with effecter organ, this junction called neuroeffector junction. Chemicals fill
this synaptic cleft, which acts as transporter of impulse between neurons forming the
junction are called neurotransmitter.
Two chemical transmitters have been established as neurotransmitter in the ANS. These are
acetylcholine and norepinephrine (nor adrenaline). Both the transmitters are synthesized
primarily in the nerve endings and stored in the synaptic vesicles and released only when
nerve impulse gets arise. Neurotransmission in the autonomic nervous system occurs at
four major sites.
Acteylcholine as a neurotransmitter released three sites these are
1. Preganglionic synapse in both parasympathetic and sympathetic ganglia.
2. Parasympathetic postganglionic neuroeffector junctions.
3. All somatic motor end plates on skeletal muscle.

Two chemical transmitters have been established as neurotransmitter in the ANS. These are
acetylcholine and norepinephrine (nor adrenaline). Both the transmitters are synthesized
primarily in the nerve endings and stored in the synaptic vesicles and released only when
nerve impulse gets arise. Neurotransmission in the autonomic nervous system occurs at
four major sites. Acteylcholine as a neurotransmitter released three sites these are
1. Preganglionic synapse in both parasympathetic and sympathetic ganglia.
2. Parasympathetic postganglionic neuroeffector junctions.
3. All somatic motor end plates on skeletal muscle.
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Norepinephrine as neurotransmitter is released at most sympathetic postganglionic

neuroeffector junctions, and the neurons that release this substance are called adrenergic
neurons. Its better that always remembers that at postgnglionic sympathetic site
norepinephrine is the transmitter except in sweat glands and some blood vessels in skeletal
muscles and for left places its acetylcholine.
The drugs that mimic the action of actetylcholine are called cholinergic or
parasympathomimetic drugs similarly the drugs mimic the action of norepinephrine are
called aderenergic or sympathomimetic drugs.
\

Books/Autonomic nervous system/Receptors

From Pharmpedia
In the transmission of nerve impulse, continuous conduction of electrical signal is required
and this done by neurochemicals by acting on receptors, which are either voltage gated or
chemical, mediated. These receptors are located on heads or tails of neuron called dendron
or on effecter organ like muscles etc. The drug receptor interaction is a signal transmission
phenomenon, could follow any of the following mechanisms for adrenergic and cholinergic
agonist and antagonist:-
1. Receptor linked to ion channels (ligand gated or voltage gated receptors)
2. Receptor controlled generation of second messenger (G-protein linked with c AMP or G
protein linked with phosphoinositide systems).

Books/Autonomic nervous
system/Cholinergic receptors
From Pharmpedia
Acetylcholine is the transmitter at three different sites, autonomic ganglia,
parasympathetic postganglionic nerve terminals and skeletal muscle motor nerve terminals.
The action of acetylcholine on visceral effectors (smooth muscle of GIT, cardiac muscle and
exocrine gland) resembles the action of the naturally occurring plant alkaloid muscarine.
Therefore these receptors of acetylcholine on visceral effectors are called muscarinic
receptors. Atropine blocks this receptor of acetylcholine. Acetylcholine in large dose exhibits
its effects through ganglionic stimulation. This response resembles the effect of naturally
occurring alkaloid nicotine. Thus, the response of acetylcholine on parasympathetic ganglia,
sympathetic ganglia and adrenal medulla and neuromuscular junction are called nicotinic
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receptors. At the skeletal muscle motor plate the cholinergic receptors are nicotinic in
nature; d-tubocurarine blocks these receptors in the skeletal muscle. The ganglionic
nicotinic receptors are blocked by hexamethonium.

M1, M2 and M3 are subtypes of muscarinic receptor. M1 receptor is G-protein coupled

receptor which is linked with IP3 /DAG. This activated system will result in increase
concentration of cytosolic calcium. And as we know calcium is responsible for long phase
depolarization in autonomic ganglia and also result in release of histamine and acid from
gland located GIT (gastrointestinal tract). Its action in CNS is unknown. M2 receptor is
located in heart which is also G- protein coupled but its activation will down regulate the
activity of c-AMP(cyclic adenosine monophosphate) and also responsible for the opening of
potassium channel as both are responsible for decreased activity because of hyper
polarization activity. As these receptors are found in heart they will decrease the generation
of impulse as a result of this decrease heart rate and slow conduction of impulses. M3 is
also IP3 /DAG linked but they are located on smooth muscle and exocrine glands will result
in the contraction of muscles and secretion from gland because it will increase the cytosolic
calcium.
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Characteristic of important subtypes of

nicotinic receptor
Nicotinic receptors are of two types’ Nm and Nn. Nm is located in neuromuscular junction
causes contraction of skeletal muscles because it causes depolarization of muscle end plate.
Nn causes depolarization in autonomic ganglia result in post ganglionic impulse. Also cause
release of catecholamine from adrenal medulla and also site specific excitation or inhibition
in brain. Both Nm and Nn are Na+ and k+ channel linked but Nn also linked with an extra
Ca++ channel.

Books/Autonomic nervous
system/Adrenergic receptors
From Pharmpedia

Fig 2.10 Signaling in sympathetic system

Fig 2.11 Secretion of Adrenal Medula

Nor epinephrine is the neurotransmitters at the sympathetic postganglionic nerve terminal

that innervate visceral effectors the stimulation of adrenoceptor on these tissues always do
not produce identical response. Therefore, based on the nature and physiological response
obtained, adrenoceptors are classified as alpha and beta-receptors. Generally alpha-
receptors are excitatory (vasoconstriction) and beta-receptors are inhibitory (vasodilatation)
in nature with the exception of heart where beta-receptors are stimulatory while in visceral
smooth muscles where alpha and beta-receptors both are inhibitory in nature. The
distribution of these receptors in different organs is also different; some organs show the
presence of one-type receptors and some are showing both type.

Fig 2.12 Mechanism of Neuro transmission

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Characteristic of important subtypes of alpha

(α) receptor
There are two types of α receptor α1 and α2. α1 is located on post junction of effecter organ
and α2 is located in prejunctional nerve ending, also postjunctional in brain, pancreatic beta
cells, platelets and extrajunctional in certain blood vessels. α1 is linked with IP3 /DAG and
phospholipase A2 which will result in increase concentration of cytosolic calcium which is
responsible for contraction of smooth muscles in blood vessels (vasoconstriction) and
arrhythmia (contraction of cardiac muscles) but one point should be noted that it is
responsible for gut smooth muscle relaxation because there two sets of muscles are
present; circular and radial if you contract one other will relax so contraction of circular
muscle results in gut relaxation. IP3 /DAG also result in activation of protein kinases, which
signal nucleus for formation of specific proteins which are responsible for gland secretion.
α2 is also linked with IP3 /DAG which will result in increase concentration of cytosolic
calcium but is also linked with c AMP which is down regulated mood because of opening of
k+ channel and closing of Ca2+ channel or blocking of calcium channel. As α2 is located in
prejunctional site of synapse it will result in reuptake of neurotransmitters i.e. decreased
depolarization or reduced activity so it’s a good target in the treatment of CNS disorders, as
it reduces the central sympathetic outflow as its linked with IP3 /DAG it results in
vasoconstriction as of α1.

Characteristic of important subtypes of beta

(β) receptor
β1, β2 and β3 are three sub types of β receptors and all are c AMP linked but differ in their
location and accordingly in their activity with an exception that β2 is linked with down
regulated c AMP so it will responsible for decreased activity. β1 is present in bronchi, blood
vessels, uterus, urinary tract and eye. β2 is located in heart and juxta glomerular cells in
kidney. β3 is present on adipose tissue and its much detail is not available. As β1 will result
in activation of protein kinases which are responsible for contraction of smooth muscles and
secretion from glands and depolarization in case nerve conduction while opposite for β2.

Books/Autonomic nervous
system/Physiology of autonomic nervous
system
From Pharmpedia

Cardiovascular system
Both sympathetic and parasympathetic nerves innervate heart. The activation of the
sympathetic outflow to the heart results in increased heart rate (tachycardia), force of
contraction (positive ionotropy) and conductivity in the atrioventricular region (A-V region).
On the other hand, activation of parasympathetic out flow of the heart results in decrease a
in heart rate (bradycardia) and prolongation in the AV conduction time.

Role of Reflex action in regulation of heart

activity
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Reflexes regularize the heart activity. When there is sudden change in mean arterial blood
pressure because of increased sympathetic activity leads to the activation of baroreceptor
reflex and increased out flow of parasympathetic system. This reflex action slows the heart.
The opposite mechanism works in case of hypotension in which parasympathetic system has
increased activity.

Reproductive system
In male sympathetic stimulation causes vasoconstriction and contraction of the smooth
muscles of the prostrate, seminal vesicles, prostatic urethra and vas deferens. The
parasympathetic system promotes vasodilatation of blood vessels of the cavernous tissue of
the penis and thus promotes penile errection therefore sympathetic system is important for
ejaculation and the parasympathetic is for the penile errection.

Gastro intestinal tract

Both sympathetic and parasympathetic nerves sympathetic stimulation to the GIT inhibits
peristaltic movements and increases the tone of the sphincter richly innervate the GIT. It
does not inhibit gastric secretion. Parasympathetic stimulation increases peristaltic activity
and the secretion of gastric and other digestive juices, but decreases the tone of sphincter.

Urinary bladder
The stimulation of sympathetic fibers innervating the vasculature of the bladder causes the
urethral orifice to close. Parasymsympathetic stimulation causes contraction of the detrusor
muscle and relaxation of the sphincter leading to emptying of the bladder. The micturation
is a complex mechanism involving autonomic nervous system and partly voluntary control.

Eye
The smooth muscles that control the size of the pupil and the degree of the visual
accommodation are supplied by autonomic nervous system. The radial muscle of the iris
(dilator papillae) is innervated by sympathetic fibers. These fibers arise from cells in the
super cervical ganglion, and their stimulation causes the contraction of the radial muscle
fibers leading to dilation of the pupil (mydriasis). The dilatation of pupil so produced is
known as active mydriasis. The circular muscle of the iris (constrictor pupillae) is innervated
by Para sympathetic nerves arising from cervical ganglia. Stimulation of the cholinergic
fibers causes contraction of the circular smooth muscle of the iris and this produces he
contraction of the pupil (miosis)
The lens, which aids in visual accommodation, is attached to the cillary body by suspensory
ligaments. When the smooth muscles of the cillary body are relaxed, the cillary body exerts
tension on the lens causing it to flatten. Now this accommodated for far vision. Stimulation
of the parasympathetic nerves causing contraction of the smooth muscles of the cilary
body; this decreases the lateral tension on the lens. The lens thickens and the eye
accommodates for near vision (cycloplegia). In this condition the pupil is widely dilated and
the power for accommodation is lost simultaneously. Cholinergic and adrenergic receptors
agonist and antagonist are very good target for treatment of various dysfunction as agonist
or antagonist like heart disorder, glaucoma, urinary dysfunction, peptic ulcer, mydriatic and
cyclopegic, preanesthetic medication Parkinson’s diseases, spasm, motion sickness etc.

Table 1. Organ and the receptors simulation

The Autonomic Nervous System

Structure Sympathetic Stimulation Parasympathetic Stimulation
Iris (eye muscle) Pupil dilation Pupil constriction
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Salivary Glands Saliva production reduced Saliva production increased
Oral/Nasal Mucosa Mucus production reduced Mucus production increased
Heart Heart rate and force increased Heart rate and force decreased
Lung Bronchial muscle relaxed Bronchial muscle contracted
Stomach Peristalsis reduced Gastric juice secreted; motility
increased
Small Intestine Motility reduced Digestion increased
Large Intestine Motility reduced Secretions and motility increased
Liver Increased conversion of .
glycogen to glucose
Kidney Decreased urine secretion Increased urine secretion
Adrenal medulla Norepinephrine and .
epinephrine secreted
Bladder Wall relaxed Wall contracted
Sphincter closed Sphincter relaxed

Fig.13 Mechanism of direct acting adrenergic drugs

Fig.14(a) Mechanism of indirect acting adrenergic drugs

Fig 14(b) Mechanism of indirect acting adrenergic drugs adrenergic

This is a free Pharmpedia textbook

Author Prof.A.N.Nagappa
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