Autonomic Nervous System (ANS) Lecture PDF

Autonomic Nervous System (ANS) Lec. -3- Part one Stage -3- Dr. Hussein Salah Rabea Introduction Nervous system CNS PNS Central Peripheral Spinal Afferent Efferent Br...

Autonomic Nervous System (ANS) Lec. -3- Part one Stage -3- Dr. Hussein Salah Rabea Introduction Nervous system CNS PNS Central Peripheral Spinal Afferent Efferent Brain N.S. (CNS) N.S. (PNS) cord P.N.S. P.N.S. Nervous system  innervate skeletal muscles Afferent PNS somatic PNS nervous system Efferent PNS Autonomic nervous system which innervates cardiac muscle, smooth muscle and glands. Autonomic Nervous System (ANS) ▪ The ANS is a division of the peripheral nervous system that regulates involuntary bodily functions. ▪ It controls involuntary physiological functions like heart rate, blood pressure, digestion, respiratory rate, and glandular secretion. ▪ It is composed of two main divisions: the sympathetic nervous system (SNS) (fight or flight) the parasympathetic nervous system (PNS). (rest and digest) ❑Autonomic nervous system is made up of two neurons: 1) Preganglionic neurons 2) postganglionic neurons ❖Preganglionic neurons The first neuron has its cell body in the CNS. The neurons passing between the CNS and the ganglia are called preganglionic neurons ; {The synapse between the two neurons is outside the CNS in a cell cluster called an autonomic ganglion.} ❖While the neuron passing between the ganglia and the effector cells are postganglionic neurons. ❑The efferent autonomic signals are transmitted to the various organs of the body through these two major subdivisions: 1.sympathetic nervous system (Adrenergic system) 2.parasympathetic nervous system (cholinergic system) ❑Each system is dominant under certain conditions. The sympathetic system predominates during emergency “fight-or-flight” reactions and during exercise. The overall effect of the sympathetic system under these conditions is to prepare the body for strenuous physical activity.  The parasympathetic system predominates during, resting conditions (“rest and digest”).. The overall effect of the parasympathetic system, under these conditions, is to conserve and store energy, and to regulate basic body functions such as digestion and urination.  Neurotransmission ❑The two most common neurotransmitters released by neurons of the ANS are: 1. acetylcholine (Ach) 2. norepinephrine (NE) ❖Neurotransmitters are synthesized in the axon and stored in vesicles for subsequent release. fibers that release acetylcholine are referred to as cholinergic fibers. fibers that release norepinephrine are referred to as adrenergic fibers.  Neurotransmission ❑Neurotransmitter, it must be rapidly removed or inactivated from the synapse or, in this case, the neuroeffector junction. This is necessary to allow new signals to get through and influence effector tissue function. ❑Neurotransmitter activity may be terminated by three mechanisms: 1. Enzymatic degradation 2. Reuptake into the neuron 3. Diffusion away from the synapse  Types of ANS receptors A. Acetylcholine binds to two types of cholinergic receptors: 1.Nicotinic receptors 2.Muscarinic receptors B. Adrenergic receptors for norepinephrine and epinephrine: 1. Alpha (α) 2. Beta (β) Parasympathetic Nervous System (PNS) Parasympathetic also called cholinergic. ❖Cholinergic fibers include: 1. All preganglionic fibers of the ANS, both sympathetic and parasympathetic systems. 2. All postganglionic fibers of the parasympathetic system. 3.Some sympathetic postganglionic fibers like sweat glands.  Neurotransmission at cholinergic neurons ❖Neurotransmission in cholinergic neurons involves six sequential steps: 1) synthesis of ACh, 2) storage, 3) release, 4) binding of Ach to the receptor, 5) degradation of ACh in the synaptic cleft (the space between the nerve endings and the adjacent receptors on nerves or effector organs), and 6) recycling of choline CHOLINERGIC RECEPTORS (CHOLINOCEPTORS) ❖Two families of cholinoceptors, A. Muscarinic receptors B. Nicotinic receptors A. Muscarinic receptors G protein-coupled receptors: Muscarinic receptors belong to this class of receptors. Muscarine and ACh: These receptors bind to both muscarine (from poisonous mushrooms) and acetylcholine. Nicotine affinity: Muscarinic receptors have a weak affinity for nicotine. Subclasses: There are five subclasses of muscarinic receptors, but only M1, M2, and M3 have been characterized. ❖1. Location of muscarinic receptors: Autonomic effector organs: Muscarinic receptors are found on organs such as the heart, smooth muscle, brain, and exocrine glands. Neurons: All five subtypes are found on neurons. Specific locations: M1 receptors are on gastric parietal cells, M2 receptors are on cardiac cells and smooth muscle, and M3 receptors are on the bladder, exocrine glands, and smooth muscle. Drug effects: Drugs with muscarinic actions preferentially stimulate muscarinic receptors on these tissues, but at high concentrations, they may also activate nicotinic receptors. ❖2. Mechanism of acetylcholine signal transduction: G protein-coupled receptors Signal transduction: When ACh binds to a muscarinic receptor, it initiates a cascade of intracellular events mediated by G proteins. Depend on type of subtypes of receptor the action may be determine M1 and M3 receptors: Activation of these subtypes typically leads to: ▪ G protein activation: Coupling with a G protein, often of the Gq type. Phospholipase C activation: Gq proteins activate phospholipase C. Second messenger generation: Phospholipase C cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5- trisphosphate (IP3) and diacylglycerol (DAG). ▪ Cellular responses: IP3: Increases intracellular Ca2+ levels, leading to various effects like muscle contraction, secretion, and enzyme activation. DAG: Activates protein kinase C, which phosphorylates numerous proteins, influencing cellular functions.  M2 receptors: Activation of these receptors often leads to: G protein activation: Coupling with a Gi protein. Adenylyl cyclase inhibition: Gi proteins inhibit adenylyl cyclase. cAMP reduction: This results in decreased levels of cyclic adenosine monophosphate (cAMP). Cellular responses: In cardiac muscle, reduced cAMP levels lead to decreased heart rate and contractility. B- Nicotinic Receptors Nicotinic receptors are a type of ligand-gated ion channel that are activated by acetylcholine (ACh) and nicotine. They play a crucial role in neurotransmission in both the central nervous system (CNS) and the peripheral nervous system. ❑Structure and Function: Ligand-gated ion channel: Binding of ACh or nicotine to the receptor causes a conformational change that opens an ion channel. Ion influx: The channel allows the influx of sodium ions, leading to depolarization of the cell. Nicotine effects: Nicotine can both stimulate and block nicotinic receptors, depending on its concentration. Low concentrations stimulate, while high concentrations block. ❖Locations: Central nervous system (CNS): Nicotinic receptors are found in various regions of the brain and spinal cord. Adrenal medulla: They are present in the adrenal medulla, where they play a role in the release of catecholamines. Autonomic ganglia: Nicotinic receptors are located in both sympathetic and parasympathetic ganglia. Neuromuscular junction (NMJ): They are found at the NMJ, where they mediate the transmission of nerve impulses to skeletal muscles. ❖Subtypes and Pharmacology: NM (neuromuscular) receptors: These receptors are specifically found at the NMJ and are responsible for muscle contraction. NN (neuronal) receptors: These receptors are located in autonomic ganglia and the CNS. Cholinergic Agonists DIRECT-ACTING CHOLINERGIC AGONISTS ❖Cholinergic agonists mimic the effects of ACh by binding directly to cholinoceptors (muscarinic or nicotinic). ❖These agents may be broadly classified into two groups: 1) choline esters, which include endogenous ACh and synthetic esters of choline, such as carbachol and bethanechol, and 2) naturally occurring alkaloids, such as nicotine and pilocarpine  All direct-acting cholinergic drugs have a longer duration of action than ACh…….? The more therapeutically useful drugs (pilocarpine and bethanechol) preferentially bind to muscarinic receptors and are sometimes referred to as muscarinic agents. However, as a group, the direct-acting agonists show little specificity in their actions, which limits their clinical usefulness.  INDIRECT-ACTING CHOLINERGIC AGONISTS: ANTICHOLINESTERASE AGENTS (REVERSIBLE) ▪ AChE is an enzyme that specifically cleaves ACh to acetate and choline and, thus, terminates its actions. ▪ It is located both pre- and postsynaptically in the nerve terminal where it is membrane bound. ▪ Inhibitors of AChE (anticholinesterase agents or cholinesterase inhibitors) indirectly provide cholinergic action by preventing the degradation of ACh. ▪ This results in an accumulation of ACh in the synaptic space ▪ Therefore, these drugs can provoke a response at all cholinoceptors, including both muscarinic and nicotinic receptors of the ANS, as well as at the NMJ and in the brain.  Reversible inhibitors are physostigmine, neostigmine, pyridostigmine, edrophonium, rivastigmine, and donepeizil. The reversible AChE inhibitors can be broadly classified as short-acting or intermediate-acting agents. All are poorly absorbed from conjunctiva, skin, and lungs except physostigmine which is well absorbed from all sites. The effects are similar to direct-acting cholinergic agonists. Primary target organs of anticholinesterase drugs are eye, skeletal muscle, neuromuscular junctions, gastrointestinal tract, urinary tract, respiratory tract, and heart. ❖These agents are commonly used in the treatment of: glaucoma, myasthenia gravis, stimulation of gastrointestinal and urinary tract motility (for example, neostigmine)—same effects as with agonists, reversal of neuromuscular blockade, and atropine poisoning.  INDIRECT-ACTING CHOLINERGIC AGONISTS: ANTICHOLINESTERASE AGENTS (IRREVERSIBLE) A number of synthetic organophosphate compounds have the ability to bind covalently to AChE. The result is a long-lasting increase in ACh at all sites where it is released. Many of these drugs are extremely toxic and were developed by the military as nerve agents. Related compounds, such as parathion and malathion, are used as insecticides. THANK YOU