Dr.Anantha Naik Nagappa
1.Introduction
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 inttwparts central nervous system and peripheral nervous system; peripheral system is further divided intautonomic nervous system (ANS) and somatic nervous system. This ANS is again divided intparasympathetic nervous system and sympathetic nervous system.
1.1. 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 dnot notice when blood vessels change size or when our heart beats faster. However, some people can be trained tcontrol some functions of the ANS such as heart rate or blood pressure.
The ANS is most important in twsituations:
1. In emergencies that cause stress and require us t"fight” or take "flight" (run away and
2. In non emergencies that allow us t "rest" and "digest."
Fig. 2.1 Sympathetic and parasympathetic neurons with ganglion.
Fig. 2.2 Classification of nervous system
Autonomic is a combination of twwords autos (self) and nomos (regulating). Thus ANS has a property tregulate organ functioning automatically. Thus it could maintain the homeostasis of an organ texist. The twsubparts of ANS, parasympathetic nervous 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 tsame 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 sif sympathetic system gets activated means energy is utilized in the form of heart contraction or increased heart beat strelax the myocardial muscle parasympathetic system gets activated and relax the myocardial muscle as the demand for oxygen by the body is decreased but dremember 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 tone 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 tconserve the energy beyond the needed amount.
1.2 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 intthree parts:
- The sympathetic nervous system
- The parasympathetic nervous system
- The enteric nervous system.
2.Sympathetic system
The preganglionic neurons of the sympathetic system have their origin (cell bodies) in the thoracic and lumbar region (thoracolumabar) of the spinal cord. There are twmajor 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.
Fig. 2.3 Sympathetic nervous system
3.Parasympathetic system
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 tor in the effecter organ. The parasympathetic fibres are long while the postganglionic axons arising from parasympathetic ganglia are short.
Fig .2.4 Parasympathetic system
4.The enteric nervous system.
The enteric nervous system is a third division of the autonomic nervous system that you dnot hear much about. The enteric nervous system is a meshwork of nerve fibers that innervate the viscera (gastrointestinal tract, pancreas, and gall bladder).
Scientists whstudy the network of nerves surrounding the esophagus, stomach and intestines compare it ta microcomputer, and call the better-known brain-in-the-head a "mainframe." But while microcomputers represent the future of silicon processing, this biological micr-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: tregulate 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 tsee 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.
Fig. 2.5 Neurotransmitters in ANS
5.Neurotransmission in ANS
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.
Fig 2.6 Neurotransmission
Twchemical 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.
Fig 2.7 Signaling in sympathetic and parasympathetic systems
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.
6.Receptors
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 tion 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).
7.Cholinergic receptors
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 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.
Fig. 2.8 Characteristic of important subtypes of muscarinic receptor
M 1 , M 2 and M 3 are subtypes of muscarinic receptor. M1 receptor is G-protein coupled receptor which is linked with IP 3 /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 alsresult 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 alsG- protein coupled but its activation will down regulate the activity of c-AMP(cyclic adenosine monophosphate) and alsresponsible 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 alsIP 3 /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.
Fig 2.9 Signal transduction
7.1 Characteristic of important subtypes of nicotinic receptor
Nicotinic receptors are of twtypes’ 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. Alscause release of catecholamine from adrenal medulla and alssite specific excitation or inhibition in brain. Both Nm and Nn are Na + and k + channel linked but Nn alslinked with an extra Ca ++ channel.
8. Adrenergic receptors
Nor epinephrine is the neurotransmitters at the sympathetic postganglionic nerve terminal that innervate visceral effectors the stimulation of adrenoceptor on these tissues always dnot 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 alsdifferent; some organs show the presence of one-type receptors and some are showing both type.
Fig 2.10 Signaling in sympathetic system
Fig 2.11 Secretion of Adrenal Medula
Fig 2.12 Mechanism of Neuro transmission
8.1Characteristic of important subtypes of alpha (α) receptor
There are twtypes of α receptor α 1 and α 2 . α 1 is located on post junction of effecter organ and α 2 is located in prejunctional nerve ending, alspostjunctional in brain, pancreatic beta cells, platelets and extrajunctional in certain blood vessels. α 1 is linked with IP 3 /DAG and phospholipase A 2 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 twsets of muscles are present; circular and radial if you contract one other will relax scontraction of circular muscle results in gut relaxation. IP 3 /DAG alsresult in activation of protein kinases, which signal nucleus for formation of specific proteins which are responsible for gland secretion. α 2 is alslinked with IP 3 /DAG which will result in increase concentration of cytosolic calcium but is alslinked 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 sit’s a good target in the treatment of CNS disorders, as it reduces the central sympathetic outflow as its linked with IP 3 /DAG it results in vasoconstriction as of α 1 .
8.2Characteristic of important subtypes of beta (β) receptor
β 1 , β 2 and β 3 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 β 2 is linked with down regulated c AMP sit will responsible for decreased activity. β 1 is present in bronchi, blood vessels, uterus, urinary tract and eye. β 2 is located in heart and juxta glomerular cells in kidney. β 3 is present on adipose tissue and its much detail is not available. As β 1 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 β 2 .
9.Physiology of autonomic nervous system:-
9.1Cardiovascular system
Both sympathetic and parasympathetic nerves innervate heart. The activation of the sympathetic outflow tthe 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.
9.2Role of Reflex action in regulation of heart activity:-
Reflexes regularize the heart activity. When there is sudden change in mean arterial blood pressure because of increased sympathetic activity leads tthe 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.
9.3Reproductive 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.
9.4Gastrintestinal tract
Both sympathetic and parasympathetic nerves sympathetic stimulation tthe 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.
9.5Urinary bladder
The stimulation of sympathetic fibers innervating the vasculature of the bladder causes the urethral orifice tclose. Parasymsympathetic stimulation causes contraction of the detrusor muscle and relaxation of the sphincter leading temptying of the bladder. The micturation is a complex mechanism involving autonomic nervous system and partly voluntary control.
9.6Eye
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 tdilation of the pupil (mydriasis). The dilatation of pupil sproduced 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 tthe 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 tflatten. 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 SEQ Table \* ARABIC 1 . Organ and the receptors simulation
The Autonomic Nervous System | ||
Structure |
Sympathetic Stimulation |
Parasympathetic Stimulation |
Iris (eye muscle) |
Pupil dilation |
Pupil constriction |
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 |
|
Kidney |
Decreased urine secretion |
Increased urine secretion |
Adrenal medulla |
Norepinephrine and |
|
Bladder |
Wall relaxed |
Wall contracted |
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