Autonomic Nervous System PDF

Physiology-1 Prof. Basel A Abdel-Wahab Autonomic N.S. Physiology Prof. Basel A Abdel-Wahab Professor of Molecular & Clinical Pharmacology and Toxicology  Physiology-1 Prof. Basel A Abdel-Wahab Lear...

Physiology-1 Prof. Basel A Abdel-Wahab Autonomic N.S. Physiology Prof. Basel A Abdel-Wahab Professor of Molecular & Clinical Pharmacology and Toxicology  Physiology-1 Prof. Basel A Abdel-Wahab Learning outcomes (Los) By the end of the lecture, you should be able to:  State the divisions of the nervous system.  State the autonomic ganglia and its function.  Explain the concept of synapse and its functions.  Enumerate the different types of neurons  Explain the different properties of neurons.  Physiology-1 Prof. Basel A Abdel-Wahab AUTONOMIC NERVOUS SYSTEM NERVOUS SYSTEM  Physiology-1 Prof. Basel A Abdel-Wahab Divisions of the Nervous system Physiology-1 Prof. Basel A Abdel-Wahab Physiology-1 Prof. Basel A Abdel-Wahab Physiology-1 Prof. Basel A Abdel-Wahab  Physiology-1 Prof. Basel A Abdel-Wahab Role of Sympathetic and parasympathetic NS. 17-Mar-21 8 Physiology-1 Prof. Basel A Abdel-Wahab Physiology-1 Prof. Basel A Abdel-Wahab Physiology-1 Prof. Basel A Abdel-Wahab  Physiology-1 Prof. Basel A Abdel-Wahab The autonomic innervation of both systems consists of a myelinated preganglionic fibers 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.  Physiology-1 Prof. Basel A Abdel-Wahab Transmission in the ANS A. Electrical conduction: It carries along the intact nerve fibers where impulse propagation occurs via change in resting membrane potential results from ionic movements (Sodium influx and Potassium outflux) through voltage-gated ion channels leading to membrane depolarization and impulse transmission. B. Synaptic chemical transmission: It occurs in the regions in which there is a discontinuity of nerve fibers (synapse). It needs specific chemical transmitter that releases from presynaptic site to bind with receptors present on the postsynaptic site.  Physiology-1 Prof. Basel A Abdel-Wahab Types of Chemical transmitters: Chemical transmitter of parasympathetic N.S 1. Acetylcholine. Chemical transmitters in sympathetic N.S. 1. Norepinephrine. (Presents in the adrenergic nerve terminals) 2. Epinephrine (Adrenaline). (Presents in the adrenal medulla ONLY)  Physiology-1 Prof. Basel A Abdel-Wahab General steps of chemical transmission Chemical transmission in the ANS include : 1. Synthesis of transmitter. 2. Storage of transmitter. 3. Release of transmitter. 4. Binding with postsynaptic receptors. 5. Termination of transmission action. Physiology-1 Prof. Basel A Abdel-Wahab  Physiology-1 Prof. Basel A Abdel-Wahab 1. Acetylcholine (Ach) A) Acetyl choline (Ach) is the chemical transmitter at : 1. All autonomic ganglia whether sympathetic or parasympathetic. 2. All post ganglionic parasympathetic fibers. 3. Post ganglionic sympathetic fibers to sweat glands and some vasodilator fibers found primarily in muscles 4. The nerve endings supplying the adrenal medulla. For comparison, neuromuscular transmission is all cholinergic.  Physiology-1 Prof. Basel A Abdel-Wahab Steps of cholinergic transmission: 1. Synthesis Ach 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. Choline is obtained from plasma by active uptake mechanism drugs that inhibit this carrier can inhibit Ach biosynthesis (e.g. Hemicholinium) 2. Storage and release Ach is stored within the nerve fibers in a storage granules with choline, and ATP. Electrical stimulation of cholinergic nerve fibers enhances a process of Ca+2 dependent exocytosis and release of Ach within the synaptic cleft. Some drugs can inhibit the release of Ach hence inhibit the cholinergic transmission as: 1. Botulinum toxins 2. Some Aminoglycosides 3. Local anesthetics 4. Low Ca++ concentration.  Physiology-1 Prof. Basel A Abdel-Wahab 3. Termination Termination of Ach is only enzymatic After binding with its post synaptic receptors Acetyl choline is hydrolyzed into choline and acetic acid by the enzyme cholinesterase. There are Two main types of cholinesterases have been identified :  Physiology-1 Prof. Basel A Abdel-Wahab a) 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.  Physiology-1 Prof. Basel A Abdel-Wahab 2. Norepinephrine (NE) It is supposed to be the chemical transmitter at the post- ganglionic sympathetic fibers with the exception of the above sites mentioned with cholinergic transmission. Steps of adrenergic transmission: 1. Synthesis In the course of 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. Dopamine then enters the granules where it is converted to NE by dopamine hydroxylase. The most important mechanism of regulation of NE synthesis involves the rate limiting step, the hydroxylation of tyrosine to Dopa by tyrosine hydroxylase, which involves, in part, a feed-back inhibition  Physiology-1 Prof. Basel A Abdel-Wahab 2. Release Within storage granules, NE is combined with ATP in the ratio of 4 : 1 along with a specific protein to form an intragranular reserve pool. This reserve pool (I) is in equilibrium with intragranular mobile pool (II). NE is being released from the intragranular mobile pool in response to nerve action potential in a calcium-dependent process to activate postsynaptic α- and β-adrenergic receptors. Presynaptically there are α2-receptors that are pharmacologically distinct from the postsynaptic α1-receptors. These α2-receptors are stimulated by NE in synaptic cleft inhibiting the release of NE from adrenergic neuron. Presynaptically there are α2-receptors if stimulated by NE in synaptic cleft, it inhibits the release of NE from adrenergic neuron. Drugs acting on α2-receptors: 1. Methyl dopa. 2. Clonidine. 3. Tizanidine.  Physiology-1 Prof. Basel A Abdel-Wahab 3. Termination Termination of NE action mainly non-enzymatic. Termination of NE action occurs via 3 mechanisms: 1. Active reuptake:(95%) After exerting its effects the major part of NE is being taken up by the axon terminal by an active transport process and restored within the nerve terminal for subsequent stimulations. There are two types of active uptake mechanisms: a. Neuronal uptake (Uptake-1) in which NE is taken up in the nerve terminal. b. Extra-neuronal uptake (uptake-2) in which NE is up-taken by the post synaptic tissues. It is slower in rate and has lower role in termination of NE action than uptake -2 Some drugs can inhibit the function of uptake mechanism, allowing NE to accumulate on the postsynaptic receptors producing sympathetic stimulation e.g. Tricycic antidepressants, Cocaine  Physiology-1 Prof. Basel A Abdel-Wahab 2. Enzymatic degradation (4%) by extraneuronal catechol-O-methyltransferase (COMT). NE undergoes oxidative deamination within the cytoplasm by mitochondrial monoamine oxidase (MAO). MAO enzyme presents in two forms: 1. MAO-A: found in Liver, GIT, Plasma and CNS. It inactivates monoamines 2. MAO-B: present mainly in CNS responsible for inactivation of dopamine and 5HT. 3. Diffusion from the synaptic cleft (1%) Small part of released NE terminated by diffusion from the synaptic cleft. That part of norepinephrine which diffuses to the blood appears to be metabolized primarily by COMT present in considerable quantities in the liver and kidney.  Physiology-1 Prof. Basel A Abdel-Wahab C) Non-Adrenergic Non-Cholinergic (NANC) Transmission It has been demonstrated that autonomic responses in many organs (GIT, genitourinary tract, certain blood vessels) are 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 coined. Examples of NANC chemical messengers in the peripheral autonomic nervous system include: 1) Non peptides as ATP, adenosine, GABA, 5HT, dopamine and nitric oxide. 2)Peptides as: neuropeptides-Y (NPY), vasoactive intestinal peptide (VIP), substance P and gonadotropin releasing hormone (GnRH). Physiology-1 Prof. Basel A Abdel-Wahab  Physiology-1 Prof. Basel A Abdel-Wahab Receptors of cholinergic Transmission Physiology-1 Prof. Basel A Abdel-Wahab Physiology-1 Prof. Basel A Abdel-Wahab  Physiology-1 Prof. Basel A Abdel-Wahab Receptors of Adrenergic Transmission Physiology-1 Prof. Basel A Abdel-Wahab Thank You….