Autonomic nervous systemintroduction

a.kannout

The autonomic nervous system is a functional division of the nervous system that is largely automatic or "autonomic" in its operation and does not require conscious activation. It is concerned primarily with visceral functions which are necessary for maintenance of life such as respiration, circulation, digestion, body temperature and metabolism. The autonomic nervous system can only augment or reduce the initial functional levels. Interference with the autonomic nerve supply, therefore, does not completely abolish the vegetative functions. General Aspects of Autonomic Nervous system There are two major divisions within the autonomic nervous system: 1. The parasympathetic ANS. and 2. The sympathetic ANS. The autonomic innervation of both systems consists of a myelinated preganglionic fibre which synapse with the cell body of a second non-myelinated neuron called postganglionic fiber that in turn terminates in a synapse with the receptors of the organ supplied by it. The synapse is thus defined as a structure that is formed by the close apposition of a neuron either with another neuron (ganglion) or with effector cell (neuro-effector junction). Passage of impulse across a synapse is carried out by the process of chemical transmission while it is carried along the preganglionic or postganglionic fibers by the process of electrical conduction. General Steps of Chemical transmission:1. Synthesis of the chemical transmitter.2. Storage of chemical transmitter.3. Release of chemical transmitter by nerve impulse.4. Binding of chemical transmitter with the postsynaptic receptors.5. Termination of the action of the chemical transmitter. A. Cholinergic TransmissionA) Acetylcholine (Ach) is supposed to be the chemical transmitter at:1- All autonomic ganglia whether sympathetic or parasympathetic.2- All postganglionic parasympathetic fibers.3- Postganglionic sympathetic fibers to sweat glands and some vasodilator fibers found primarily in (sweat gland, blush area).4- The nerve endings supplying the adrenal medulla.5- Neuromuscular junction at the synapse between motor neuron and skeletal muscle.Acetylcholine is synthesized inside the nerve fiber by combination of choline with acetyl group (obtained from acetyl-CoA), a reaction catalyzed by the enzyme choline acetyltransferase. * Termination of Ach action is Only enzymatic. Acetylcholine is hydrolyzed into choline and acetic acid by the enzyme cholinesterase. Two main types of cholinesterases have been identifieda) Acetylcholinesterase (AChE) or true cholinesterase:Present in neurons and neuromuscular junction. It is responsible for the hydrolysis of Ach released in the process of cholinergic transmission. It hydrolyzes ACh at a greater velocity and it also hydrolyzes methacholine but not benzoylcholine.b) Butyrylcholinesterase (BuChE) or pseudocholinesterase: Present mainly in plasma, liver and other organs. Its physiological function is unknown. It exhibits a maximal velocity of hydrolysis with butyrylcholine as a substrate. It also hydrolyzes ACh and benzoylcholine but not methacholine.Cholinergic Receptors: There are tow types of cholinergic receptors: 1) Muscarinic Rs. 2) Nicotinic Rs. B. Adrenergic TransmissionB)Norepinephrine (NE) is supposed to be the chemical transmitter atThe postganglionic sympathetic fibers with the exception of the above sites mentioned with cholinergic transmission. Steps of Adrenergic Transmission:1. In synthesis of NE, tyrosine is being actively taken up by the adrenergic neuron where it is hydroxylated to dopa that is in turn decarboxylated to dopamine. 2. Dopamine then enters the granules where it is converted to NE by dopamine hydroxylase. 3. Only in adrenal medulla, NE is converted to Epinephrine through methylation by the enzyme catechol-O-methyl transferase.4. NE is then combined with ATP in the ratio of 4: 1 along with a specific protein to form an intragranular reserve pool. 5. NE is being released from the intragranular pool in response to nerve stimulation and influx of calcium to bind with the postsynaptic adrenergic receptors. 6. Presynaptically there is an α2-receptor that is pharmacologically distinct from the postsynaptic α-receptor. These receptors are stimulated by NE in synaptic cleft inhibiting the release of NE from adrenergic neuron (Autoregulation). The most important mechanism of regulation of NE synthesis involves the rate limiting step that is the hydroxylation of tyrosine to Dopa by tyrosine hydroxylase, which involves, in part, a feed-back inhibition.7. Termination of NE actionTermination of NE action is mainly Non-enzymatic.Termination of NE occurs by 2 processes involve :1- Active reuptake of the intact transmitter molecule Released NE can be returned to the adrenergic nerve terminal by active reuptake mechanism present in the presynaptic nerve terminals. This represents more than 95% of the termination mechanisms of NE.2. Enzymatic degradation to inactive metabolites. Released NE is also inactivated by enzymatic inactivation by the action of two enzymes:1) Monamine oxidase (MAO).2) Catechol-O-methyl transferase (COMT).It represents about 4% of total termination mechanisms of NE. C) Non Adrenergic Non Cholinergic (NANC) TransmissionIt has been demonstrated that autonomic responses in many organs (GlT, genitourinary tract, certain blood vessels) arc unaffected or not completely blocked by adrenergic and cholinergic antagonists. This has been taken as evidence for the existence of substances other than norepinephrine and acetylcholine that are involved in autonomic transmission and the term Non Adrenergic Non Cholinergic(NANC) transmission was used. Examples of NANC chemical messengers in the peripheral autonomic nervous system include:I- Non peptides as: ATP, adenosine, GABA, 5HT, dopamine and nitric oxide.2-Peptides as: neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P and gonadotropin releasing hormone (GnRH).These substances may function as primary transmitters or modulate the response that follows preganglionic nerve stimulation

Dr.Ahmad

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a.kannout

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