Anatomy and Physiology of PNS PDF

Welcome To Basic principles of pharmacology YFRM202 MBChB II 1  Welcome To This Topic Anatomy and Physiology of the Peripheral Nervous System D YFRM202 2 Learning Outcomes At the end of this...

Welcome To Basic principles of pharmacology YFRM202 MBChB II 1  Welcome To This Topic Anatomy and Physiology of the Peripheral Nervous System D YFRM202 2 Learning Outcomes At the end of this lecture, you should be able to: Describe the anatomy and physiology of the Peripheral nervous system (PNS) and its subdivisions. Describe the organ system effects of the divisions of the autonomic nervous system (ANS). Describe the structures, neurotransmitters and receptors of the PNS. Describe the locations of the different receptors and their effects if stimulated. 3 Divisions of the Nervous System Image source: BioNinja, 2024. Autonomic Control. [online] Available at: https://ib.bioninja.com.au/options/option-a-neurobiology-and/a2-the-human- brain/autonomic-control.html [Accessed 7 Sep. 2024]. The ANS, unlike the somatic nervous system, is not under voluntary control 4  Sympathetic ‘Fight or Flight’ Reaction Activation of the sympathetic nervous system produces the “fight or flight” reaction in response to threatening situations. Cardiovascular stimulation provides muscles with oxygen and fuels required to support vigorous physical activity, and activation of glycogenolysis and lipolysis releases the necessary energy substrates. Think of the effects from an Sympathetic neurons innervate and inhibit “adrenaline rush” neurotransmitter release from parasympathetic neurons Brenner & Stevens’ Pharmacology.2023.Chapter 6, pages 59-73. 5  Parasympathetic ‘ Rest and Digest’ System The parasympathetic nervous system is sometimes called the “rest and digest” system because it slows the heart rate and promotes vegetative functions, such as digestion, defecation, and micturition. Many parasympathetic effects (including pupillary constriction, bronchoconstriction, and stimulation of gut and bladder motility) are caused by smooth muscle contraction. In addition to their effects on innervated tissues, parasympathetic neurons innervate and inhibit neurotransmitter release from sympathetic neurons. Brenner & Stevens’ Pharmacology.2023.Chapter 6, pages 59-73. 6 Opposing Effects of the ANS In many instances, the sympathetic and parasympathetic divisions can be viewed as physiological antagonists, having opposing effects on organ functions. Both systems are tonically active → antagonism of one system results in enhanced activity of the other. Most viscera are innervated by both divisions of the autonomic nervous system, and their activities on specific structures may be either discrete and independent or integrated and interdependent. Goodman & Gilman's: The Pharmacological Basis of Therapeutics – Chapter 10 Brenner & Stevens’ Pharmacology.2023.Chapter 6, pages 59-73. Netter’s Illustrated Pharmacology – page 35 7 Autonomic System Effects on Organ Systems Image source: iMotions, 2022. Sympathetic and Parasympathetic Nervous Systems. [online image] Available at: https://imotions.com/wp- content/uploads/2022/10/Sympathetic-parasympathetic-nervous-systems.png [Accessed 7 Sep. 2024]. 8 Summary of Organ System Effects on Activating the Sympathetic System Rang & Dale’s Pharmacology.2024. Chapter 15, pages 205-224:Table 15.1 9  Summary of Organ System Effects on Activating the Parasympathetic System 10 Structure of the Autonomic Efferent Pathway Parasympathetic postganglionic neurons All preganglionic neurons release ACh, which binds to M (Muscarinic) leaving the CNS release receptors on the effector organ ACh, which binds to NN (Nicotinic) receptors Sympathetic postganglionic neurons release on the dendrites of NA, which binds to α or ß receptors on the postganglionic neurons effector organ Netter’s Illustrated Pharmacology - page 47 Rang & Dale’s Pharmacology.2024. Chapter 15, pages 205-224. 11  ANS Structure The efferent pathways in the ANS consist of 2 neurons in series: A preganglionic and a postganglionic neuron which synapse in an autonomic ganglion The sympathetic division of the autonomic nervous system is also known as the thoracolumbar division Nerves arise from the thoracic and lumbar spinal cord Most of the ganglia are located in the paravertebral chain adjacent to the spinal cord The sympathetic efferent pathway thus consists of a short preganglionic fiber and a long postganglionic fiber A few prevertebral ganglia (the celiac, splanchnic, and mesenteric ganglia) are located more distally to the spinal cord The parasympathetic division of the autonomic nervous system is also known as the craniosacral division Nerves arise from the cranial nerves III, VII, IX, and X (the oculomotor, facial, glossopharyngeal, and vagus nerves, respectively) as well as some nerves originating from the sacral spinal cord The ganglia for the parasympathetic nervous system are often located in the innervated organs The parasympathetic efferent pathway thus consists of long preganglionic fibers and short postganglionic fibers Netter’s Illustrated Pharmacology - page 35 Brenner & Stevens’ Pharmacology – page 59 12 Rang & Dale’s Pharmacology – page 164 – Figure 13.1 12 Autonomic and Somatic Efferent Pathways Single motor neuron from the CNS to the NMJ – Note NM receptors Long preganglionic parasympathetic fibres with short postganglionic parasympathetic fibres Short preganglionic sympathetic fibres with longer postganglionic sympathetic fibres Goodman & Gilman's: The Pharmacological Basis of Therapeutics – Chapter 10 – Figure 10.2 Comparative features of somatic motor nerves and efferent nerves of the autonomic nervous system. The principal neurotransmitters, ACh and NE, are shown in red. The receptors for these transmitters, nicotinic (N) and muscarinic (M) cholinergic receptors, α and β adrenergic receptors, are shown in green. Somatic nerves innervate skeletal muscle directly at a specialized synaptic junction, the motor end plate, where ACh activates Nm receptors. Autonomic nerves innervate smooth muscles, cardiac tissue, and glands. Both parasympathetic and sympathetic systems have ganglia, where ACh is released by the preganglionic fibres; ACh acts on Nn receptors on the postganglionic nerves. ACh is also the neurotransmitter at cells of the adrenal medulla, where it acts on Nn receptors to cause release of EPI and NE into the circulation. ACh is the dominant neurotransmitter released by postganglionic parasympathetic nerves and acts on muscarinic receptors. The ganglia in the parasympathetic system are near or within the organ being innervated, with generally a one-to-one relationship between pre- and postganglionic fibres. NE is the principal neurotransmitter of postganglionic sympathetic nerves, acting on α or β adrenergic receptors. Autonomic nerves form a diffuse pattern with multiple synaptic sites. In the sympathetic system, the ganglia are generally far from the effector cells (e.g., within the sympathetic chain ganglia). Preganglionic sympathetic fibres may make contact with a large number of postganglionic fibres. 13  Enteric Nervous System The enteric nervous system (ENS) consists of a network of nerves located in the gut wall that regulates gastrointestinal motility (peristalsis) and glandular secretion. The ENS is innervated by the sympathetic and parasympathetic nervous systems and is composed of the submucosal, myenteric, and subserosal nerve plexuses. Parasympathetic stimulation typically activates the ENS, whereas sympathetic stimulation inhibits the ENS. The ENS has sufficient integrative capabilities to allow it to function independently of the CNS. Brenner & Stevens’ Pharmacology – page 60 14 Neurotransmitters in the ANS Acetylcholine = Ach Noradrenaline = NA Source: Rang & Dale’s Pharmacology – Figure 13.2 Goodman & Gilman's: The Pharmacological Basis of Therapeutics – Chapter 10 Rang & Dale’s Pharmacology - Page 164-165 – Figure 13.2 15 Classifications of Autonomic Nerves and Receptors AUTONOMIC NERVES AUTONOMIC RECEPTORS Autonomic nerve fibres are Cholinoceptors are classified based on the receptors that respond to the neurotransmitter released binding of ACh to them by that neuron: Adrenoceptors are Cholinergic neurons receptors that respond to the release ACh binding of NA or adrenaline Adrenergic neurons to them release NA Brenner & Stevens’ Pharmacology - page 59 Basic & Clinical Pharmacology – Chapter 6 16 Classification of Autonomic Nervous System Source: Rang & Dale’s Pharmacology – Figure 13.2 Rang & Dale’s Pharmacology - Page 164 – Figure 13.2 Acetylcholine and noradrenaline as transmitters in the peripheral nervous system. The two main types of acetylcholine (ACh) receptor, nicotinic (nic) and muscarinic (mus) (see Ch. 14) and two types of adrenoceptor, α and β (Ch. 15), are indicated. NA, noradrenaline (norepinephrine). 17 Cholinergic Receptors Nicotinic Muscarinic (G-protein coupled receptors) (Ligand-gated ion channels) Nm (muscle M1 – M5 Nn (neuronal type) type) Found in autonomic Each subtype is Found at the ganglia, adrenal found in distinct NMJ locations medulla, throughout PNS Goodman & Gilman's: The Pharmacological Basis of Therapeutics – Chapter 10 18  Cholinergic Receptors ACh Binds to: M1,3,5 NN; NM Gαq M2,4 Gαi Phospholipase C Inhibits Smooth muscle -> Adenylyl contraction DAG Cyclase.In Vascular endo IP3 thelial cells – NO Opens K+ Opens Na+/K+ release -> Relaxation; channels ATP cAMP channels → Exocrine glands -> Ca2+ → IPSP depolarization secretion Basic & Clinical Pharmacology - Table 6.2 - Major autonomic receptor types Brenner & Stevens’ Pharmacology – page 63 Muscarinic receptors are G-Protein coupled receptors. Stimulation of M2 and M4 receptors are coupled with Gαi proteins leading to the activation of guanine nucleotide- binding proteins ( i.e. G protein α replaces GDP with GTP), which then acts to increase or decrease the formation of other second messengers. The M1, M3, and M5 receptors are coupled with Gαq proteins, and their activation stimulates phospholipase C, leading to the formation of inositol triphosphate (IP3) and diacylglycerol (DAG) from membrane phospholipids. In smooth muscles, IP3 increases calcium release from the sarcoplasmic reticulum and promotes muscle contraction. In exocrine glands, IP3 causes calcium release and glandular secretion. In vascular endothelial cells, IP3-activated calcium release stimulates nitric oxide synthesis, leading to vascular smooth muscle relaxation. The M2 and M4 receptors are coupled with Gαi proteins; their activation decreases cyclic adenosine monophosphate (cAMP) levels by inhibiting adenylate cyclase and increasing potassium efflux. This creates an inhibitory postsynaptic potential (IPSP) that makes a postsynaptic neuron less likely to generate an action potential.The effects produced by activation of muscarinic receptors are summarized in Brenner & Stevens’ Pharmacology - Table 6.2 19  Muscarinic Receptors Table 14.2 Muscarinic receptor subtypes DAG, diacylglycerol; epsp, excitatory postsynaptic potential; IP 3 , inositol trisphosphate Rang and Dale’s pharmacology, 2024.Chapter 14, pages182-204. 20 Cholinergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024. Chapter 14, pages182-204. 21  Cholinergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024. Chapter 15, 205-224: Table 15.1 22  Cholinergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024 Page 165 - Table 13.1 23 Adrenergic Receptors Source: Netter’s Illustrated Pharmacology – Figure 2.4 Netter’s Illustrated Pharmacology – page 53 - Figure 2.4 Goodman & Gilman's: The Pharmacological Basis of Therapeutics – Chapter 10 Basic & Clinical Pharmacology - Table 10.6 24 Receptors in the ANS: Adrenergic Receptors Basic & Clinical Pharmacology - Table 10.6 – Characteristics for adrenergic receptor subtypes (all G-protein coupled receptors) Brenner & Stevens’ Pharmacology – page 84 25  Adrenergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024. Chapter 15,pages 205-224: Table 15.1 26  Adrenergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024 Page 165 - Table 13.1 27  Adrenergic Effects Table 13.1 The main effects of the autonomic nervous system a The adrenoceptor and cholinoceptor types shown are described more fully in Chapters 14 and 15. Transmitters other than acetylcholine and noradrenaline contribute to many of these responses (see Table 13.2 ). b Vasodilator effects of M 3 receptors are due to nitric oxide release from endothelial cells (see Ch. 21 ). c No direct innervation. Effect mediated by circulating adrenaline released from the adrenal medulla. Rang & Dale’s Pharmacology. 2024. 15, 205-224: Table 15.1 28 Autonomic System Effects on Organ Systems Image source: Imotions. 2023. An introduction to the sympathetic and parasympathetic nervous system by Roxanna Salim, November 2019 Available at: https://imotions.com/wp-content/uploads/2022/10/Sympathetic- parasympathetic-nervous-systems.png (Date accessed: 8 September 2023) 29  Checklist Can you...  Describe the anatomy and physiology of the Peripheral nervous system (PNS) and its subdivisions?  Describe the organ system effects of the divisions of the autonomic nervous system (ANS)?  Describe the structures, neurotransmitters and receptors of the PNS?  Describe the locations of the different receptors and their effects if stimulated? 30  References Brenner and Steven’s pharmacology. 2023.Chapter 6. Parasympathetic, Neuromuscular Pharmacology, and Cholinergic Agonists. Pages 59-73 & Chapter 7. Cholinergic Receptor Antagonists. Pages 75-81. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition.Chapter 10. Rang and Dale’s pharmacology. 2024. Chapter 14. Cholinergic transmission. Pages182-204 & Chapter 15. Noradrenergic transmission. Pages 205-224. Reinhold, J. and Bourne, N. (2011) Netter’s Illustrated Pharmacology. 2nd edn.Page 35. Katzung, B.G., Trevor, A.J., & Kruidering-Hall, M. (2021) Basic & Clinical Pharmacology. 15th edn. Chapter 6. 31 32 33