Introduction

The motor portion of the Autonomic Nervous System is the major pathway for information transmission from the Central Nervous System to the involuntary effector tissue which includes smooth muscles, cardiac muscles and exocrine glands. Its major subdivision are the parasympathetic autonomic nervous system and sympathetic autonomic nervous system. The enteric nervous system is a semiautonomous part of the autonomic nervous system located in the gastrointestinal tract, with specific functions for the control of this organ system. The enteric nervous system consist of myenteric plexus and submucous plexus which they send sensory input to the parasympathetic and sympathetic nervous system and receive motor output from them. There are 3 main parts of the Autonomic Nervous System, which are : Central Roots Of Origin The parasympathetic preganglionic motor fibers originate in cranial nerve nuclei and in sacral segment of the spinal cord. The preganglionic fibers originate in the thoracic and lumbar segments of the cord.

Location Of Ganglia Most of the sympathetic ganglia are located in 2 paravertebral chains that lies along the spinal column. A few are located on the anterior aspect of the abdominal aorta. Most of the parasympathetic ganglia are located in the organs innervated, more distant from the spinal cord. Because of the location of the ganglia, the preganglionic sympathetic fibers are short and the post ganglionic fibers are long. The opposite is true for the parasympathetic system and for preganglionic fibers are long and post ganglionic fibers are short.

Uninnervated Receptors Receptors that responds to autonomic transmitters and drugs receive no innervation. These includes muscarinic receptors on the endothelium of blood vessels and some presynaptic receptors and in some species the adrenoceptors on apocrine sweat glands meanwhile Alpha 1 and Beta adrenoceptors in blood vessel.

Neurotransmitter

Neurotransmitters are chemical agents secreted at the end of axons of nerve cells that diffuse across the synaptic gap and transmit information to adjoining cells such as neurons, muscle cells, and glands, by altering their electrical state or activity. There are many neurotransmitters with a variety of structures and functions; two of the principle ones are acetylcholine and norepinephrine. Since the neurotransmitters convey information, anything that affects their behavior affects the function of the organism. Common list of neurotransmitters Serotonin which is synthesized from amino acid L-tryptophan Norepinephrine which is synthesized from Dopamine Epinephrine which is synthesized from Norepinephrine GABA which is synthesized from glutamate Histamine which is synthesized from L-histidine Glutamate and Aspartate known as excitatory neurotransmitter.

Cholinergic Transmission

Acetylcholine is the primary transmitter in all autonomic ganglia and at the parasympathetic postganglionic neuron effector cell synapses. It also the

primary transmitter at the somatic skeletal muscle neuromuscular junction. It involves 4 processes which are : Synthesis and storage Acetylcholine is synthesized from acetyl-CoA and choline by the enzyme choline acetyl-transferase. The rate limiting step is probably the transport of choline into nerve terminal. This transport can be inhibited bt the drug known as hemicholinium. Acetylcholine is actively transported into its vessicle for storage by vessicle associated transporter, VAT. This process can be inhibited by another drug known as Vesamicol

Release of Acetylcholine Release of transmitter stores from vesicles in the nerve ending requires the entry of calcium through calcium channels and triggering of an interaction between proteins associated with the vesicles which is known as vesicleassociated membrane proteins or VAMPs.and proteins which are associated with the nerve ending membrane. This interaction results in the fusion of the membranes of the vesicles with the nerve ending membranes, the opening of a pore to the extracellular space and release of the stored transmitter. The several types of botulinum toxins enzymaticaly alter synaptobrevin or one of the other docking or fusion proteins to prevent the relase process. Termination of action of Acetylcholine The action of acetylcholine in the synapse is normally terminated by metabolism to acetate and choline by the enzyme acetylcholinesterase in the synaptic cleft. The product are not excreted but are recycled in the body. Inhibition of acetylcholinesterase is an important therapeutic effect of several drugs. Drug effect on synthesis, storage, release, and termination of action of Acetylcholine Drugs that block the synthesis of Acetylcholine for an example hemicholinium, and its storage for an example vesamicol or its release for an example botulinium toxins are not useful for systemic therapy because their effects are not sufficiently selective, however because of the botulinium toxins is a very large molecule and diffuses very slowly and it can be used by injection for local effects.

Adrenergic Transmission

Norepinephrine is the primary transmitter at the sympathetic postganglionic neuron effector cell synapses in most tissue. Important exceptions include sympathetic fibers to thermoregulatory sweat glands and probably vasodilator

sympathetic fibers in skeletal muscle which release Acetylcholine. Dopamine may be a vasodilator transmitter in renal blood vessels. Andrenergic Transmission consist of 3 major functions which are : Synthesis and Storage The synthesis of dopamine and Norepinephrine is more complex than that of Acetylcholine. Tyrosine is hydroxylated by Tyrosine Hydroxylase to Dihydroxyphenylalanine which is also known as DOPA, later it will be decarboxylated into dopamine, and inside the vessicleit will be hydroxylated into norepinephrine. Tyrosine hydroxylase can be inhibited by metyrosine. Norepinephrine and Dopamine are transported into vessicles and stored there. Monoamine oxidase is present on mitochondria in the andrenergic nerve ending and inactivates a portion of the dopamine and norepinephrine in the cytoplasm. Therefore, monoamine oxidase inhibitors may increse the stores of these transmitters and other amines in the nerve endings. The vesicular transporter can be inhibited by Reserpine. Release and Termination of action. Dopamine and Norepinephrine are released from their nerve ending by the same calcium dependant mechanism responsible for Acetylcholine release. Termination of action, however, is quite different. Metabolism is not responsible for termination of action of the cate-cholamine transmitters, norepinephrine and dopamine. Instead diffusion and reuptake reduce their concentration in the synaptic cleft and stop their action. Outside the cleft, these transmitters can be metabolized monoamine oxidase and catechol -omethyltranferase and the product of this enzymatic reaction are excreted. Determination of the 24 hours excretion of metanephrine, normetanephrine, 3methoxy-4hydroxymandelic acid and other metabolites provides a measure of the total body production of catecholamine, a determination useful in diagnosing, conditions such as pheochromocytoma. Inhibition of Monoamine oxidase increases the store of catecholamine and has both therapeutic and toxic potential. Drug effects on adrenergic transmission Drus that block norepinephrine synthesis or catecholamine storage or release have been used in several disease such as pheochromocytoma and hypertension because they block sympathetic but parasympathetic function.

Cholinoceptors

Cholinoceptors is also refered as cholinergic receptors, these molecules respond to acetylcholine and its analog. Cholinoceptors are subdivided into 2 which are Muscarinic receptors As their name suggest these receptors respond to muscarinic as well as to acetylcholine. The effects of activation of these receptors resemble those of postganglionic parasympathetic nerve stimulation. Muscarinic receptors are located primarily on autonomic effector cells including heart, vascular endothelium, smooth muscle, presynaptic nerve terminals and exocrine glands Nicotinic receptors These receptors are parts of ion channels and respond to acetylcholine and nicotine, another acetylcholine mimic, but not to muscarinic. These 2 major nicotinic subtypes are located in ganglia and in skeletal muscle end plate. The nicotinic receptors are the primary receptors for transmission at these sites.

Adrenoceptors

Adrenoceptors also referred as adrenergic receptors, adrenoceptors are divided into several subtypes which are : Alpha receptors It is located on smooth muscles, presynaptic nerve terminals. blood platelets, fat cells and neurons in the brain. Alpha receptors are futher divided into 2 major type alpha 1 and alpha 2. These 2 subtypes constitute different families and utilize different G coupling proteins. Beta receptors These receptors are located on most type of smoothe muscle, cardiac muscle, some presynaptic nerve terminals and lipocyte as well as in the brain. Beta receptors are divided into 3 major subtypes which are Beta-1, Beta-2, and Beta-3. These subtypes are rather similar and utilize the same G coupling protein.

Dopamine

Dopamine is a neurotransmitter. It is a chemical messenger that helps in the transmission of signals in the brain and other vital areas. Dopamine is found in humans as well as animals, including both vertebrates and invertebrates. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area. It is a neurohormone that is released by the hypothalamus. Its action is as a hormone that is an inhibitor or prolactin release from the anterior lobe of the pituitary.Five subtypes of mammalian dopamine receptors are grouped into two classes.

D1-like receptor class This comprises of D1 and D5 receptor subtypes D2-like receptor class This comprises of D2, D3, and D4 receptor subtypes

These receptors have similar signalling properties. They however have different signal transduction pathways that determine their subtypes and classes. All of the dopamine receptors are G protein-coupled receptors ,signalling is primarily mediated by interaction with and activation of GTP-binding proteins Members of this super family are also called 7-transmembrane receptors because they traverse the cell membrane seven times. Dopamine cannot cross the blood-brain barrier, so dopamine given as a drug does not directly affect the central nervous system.

Conclusion

The autonomic nervous system is an involuntary division of the nervous system that consists of motor neurons that conduct impulses from the brain stem or spinal cord to cardiac muscle, smooth muscle and glands. These motor neurons are responsible

for regulating heart rate, regulating peristalsis, and the release of secretions from certain glands, such as the salivary glands in the mouth. General Characteristics of the Autonomic Nervous System: It is a two-neuron pathway. Sensory signals from viscera and skin send signals to autonomic neurons in brain and spinal cord. A preganglionic neuron cell body is located within the CNS. Preganglionic fibers synapse with a ganglionic neuron located in the PNS A postganglionic fiber terminates on the effector organ.

Divisions of the ANS : Sympathetic Division Parasympathetic Division Comparison between Sympathetic and Parasympathetic division:

Sympathetic division : Location of Preganglionic neurons T1 - L2 in the lateral horns of the gray matter of the spinal cord. Preganglionic neurons send fibers out the ventral root. They leave the spinal nerves through the myelin and enter the sympathetic trunk. Ganglionic neurons are located within the sympathetic chain ganglia or in collateral ganglia outside of the sympathetic trunk. Postganglionic fibers leave the sympathetic trunk through the gray rami and pass through the spinal nerve again before terminating on the effector organ. Preganglionic fibers are short and myelinated. Postganglionic fibers are long and unmyelinated. The sympathetic division is responsible for vasomotor tone Parasympathetic division : Location of preganglionic neurons in brain stem,S2, S3, and S4. Preganglionic fibers travel through cranial nerves III, VII, IX, and X, and spinal nerves S2-S4, and synapse with peripheral ganglia located very near or directly on the effector organ. Ganglionic neurons are located within peripheral ganglia. Preganglionic fibers are long and myelinated. Postganglionic fibers are short and not myelinated. Parasympathetic fibers do not control the diameter of the systemic arterioles but are responsible for peristalsis.