Autonomic Nervous System PDF

NOTES NOTES AUTONOMIC NERVOUS SYSTEM ▪ Part of peripheral nervous system ▪ Preganglionic neurons → preganglionic (PNS); regulates basic visceral processes fibers → synapse with autonomic ganglia necessary to home...

NOTES NOTES AUTONOMIC NERVOUS SYSTEM ▪ Part of peripheral nervous system ▪ Preganglionic neurons → preganglionic (PNS); regulates basic visceral processes fibers → synapse with autonomic ganglia necessary to homeostasis (postganglionic neurons) → postganglionic ▪ Autonomic nervous system (ANS) affects fibers → target organ visceral organs, glands, involuntary muscles → regulates heart rate, respiration rate, Preganglionic neurons digestion, urination, salivation, sexual ▪ General visceral efferent (GVE) neurons arousal, etc. ▪ Located in central nervous system (CNS) ▪ Divided into two systems (spinal cord) ▫ Sympathetic, parasympathetic ▪ Release acetylcholine (ACh) ▪ Unlike somatic nervous system, in ANS Postganglionic neurons ▫ Neurotransmitters synthesized, stored, ▪ GVE, general visceral afferent (GVA) released in varicosities (analogous to neurons presynaptic nerve terminals in somatic ▪ Located outside central nervous system nervous system) ▪ Release acetylcholine/norepinephrine/ ▫ Target organ’s tissue can be innervated neuropeptides by multiple postganglionic neurons ▫ Postsynaptic receptors widely scattered Autonomic ganglia on target organ ▪ Contain neuron cell body clusters (postganglionic neurons) NEURONS ▪ Synapse points between preganglionic ▪ Two neuron types in both sympathetic, fibers, postganglionic fibers parasympathetic systems ▫ Preganglionic, postganglionic SYMPATHETIC NERVOUS SYSTEM osms.it/sympathetic-nervous-system ▪ ANS component; controls visceral functions Postganglionic neurons requiring fast response (i.e. “fight or flight”) ▪ Located close to spinal cord ▪ Ganglia close to spinal cord → short ▫ Paravertebral ganglia (cervical, thoracic, preganglionic fibers, long postganglionic rostral lumbar, caudal lumbar, pelvic fibers ganglia) ▫ Prevertebral ganglia (celiac, aorticorenal, Preganglionic neurons superior mesenteric, inferior mesenteric ▪ Located: thoracolumbar spinal cord’s ganglion) intermediate horn (T1–L2) ▫ Chromaffin cells of adrenal medulla ▪ Cholinergic neurons → release ACh (modified sympathetic ganglion) OSMOSIS.ORG 445  ▪ Either adrenergic/cholinergic Sympathetic nervous system effects ▫ Adrenergic neurons → release ▪ Cardiovascular: ↑ heart rate, ↑ cardiac norepinephrine/epinephrine (adrenal output, vasoconstriction medulla) ▪ Respiratory: bronchodilation ▫ Cholinergic → release ACh ▪ Gastrointestinal: ↓ motility, ↓ secretions ▪ Effector organ receptors: ɑ1, ɑ2, β1, β2, β3 ▪ Genitourinary: ↓ bladder’s detrusor muscle activity, ejaculation ▪ Metabolic: ↑ gluconeogenesis ▪ Glands: ↓ salivation, ↑ sweating ▪ Pupils: mydriasis Figure 51.1 Neurons originating in the hypothalamus synapse with sympathetic pre-ganglionic cells bodies in spinal cord nuclei. Some pre-ganglionic neurons synapse in the paravertebral ganglia of the sympathetic chain; others synapse in the pre-vertebral ganglia. Figure 51.2 Sympathetic preganglionic neurons release acetylcholine, which bind to nicotinic receptors on postganglionic neurons. Postganglionic neurons release catecholamines, which are received by adrenergic receptors on target organs. 446 OSMOSIS.ORG  Chapter 51 Neurology: Autonomic Nervous System PARASYMPATHETIC NERVOUS SYSTEM osms.it/parasympathetic-nervous-system ▪ ANS component controls visceral functions ▪ Mostly cholinergic, but some non- not requiring fast response (i.e. “rest and adrenergic, non-cholinergic → release digest”) neuropeptides ▪ Ganglia close to target organ → long ▪ Effector organ receptors are muscarinic preganglionic fibers, short postganglionic fibers Parasympathetic nervous system effects ▪ Cardiovascular: ↓ heart rate, ↓ cardiac Preganglionic neurons output ▪ Located in brainstem (nuclei of cranial ▪ Respiratory: bronchoconstriction nerves II, VII, IX, X), sacral spinal cord (S2– ▪ Gastrointestinal: ↑ motility, ↑ secretions S4) ▪ Genitourinary: ↑ bladder’s detrusor muscle ▪ Cholinergic neurons → release ACh activity, erection Postganglionic neurons ▪ Metabolic: ↓ glycogenesis ▪ Located close to target organs ▪ Glands: ↑ salivation ▫ Ciliary ganglion (cranial nerve III) ▪ Pupils: miosis ▫ Submandibular ganglion (cranial nerve VII) ▫ Otic ganglion (cranial nerve IX) ▫ Near/inside target organ (cranial nerve X, sacral nerves) Figure 51.3 Neurons originating in the hypothalamus synapse with parasympathetic pre- ganglionic cells bodies in brainstem, spinal cord at levels S2, S3, and S4. Pre-ganglionic neurons synapse in cranial ganglia and near/in target organ. OSMOSIS.ORG 447  Figure 51.4 Summary of parasympathetic components of cranial nerves III (oculomotor), VII (facial), and IX (glossopharyngeal). Figure 51.5 Parasympathetic preganglionic neurons release acetylcholine, which binds to nicotinic receptors on the post-ganglionic neuron. The post-ganglionic neuron also releases acetylcholine, which binds to muscarinic (G-protein coupled) receptors on target organs. 448 OSMOSIS.ORG Chapter 51 Neurology: Autonomic Nervous System OSMOSIS.ORG 449  ADRENERGIC RECEPTORS osms.it/adrenergic-receptors ▪ Metabotropic receptors: respond β2 adrenergic receptors (stimulatory effect) to catecholamines (norepinephrine, ▪ Skeletal muscle blood vessels → epinephrine) vasodilation ▪ Located on sympathetic effector ▪ Bronchioles → relaxation organs → stimulated → sympathetic/ ▪ Pancreas → ↑ secretion sympathomimetic response ▪ Liver → ↑ glycogenolysis, ↑ ▪ Types gluconeogenesis ▫ ɑ, β adrenergic receptors: ɑ1, ɑ2, β1, β2, β3 β3 adrenergic receptors (stimulatory effects) ɑ1 Adrenergic receptors (stimulatory ▪ Adipose tissue → lipolysis, thermogenesis effect) ▪ Detrusor muscle → relaxation ▪ Gastrointestinal tract blood vessels, skin blood vessels → vasoconstriction Adrenergic receptor mechanism ▪ Bladder, gastrointestinal (GI) tract ▪ Catecholamines binding → Gq (stimulatory) sphincters → contraction or Gi (inhibitory) protein activation ▪ Radial (dilator) muscle of iris → contraction → second messenger cascade → ↑ ▪ Pancreas → ↓ secretion phospholipase C or ↓ adenylate cyclase → ▪ Liver → ↑ glycogenolysis effect ▪ ɑ1 adrenergic receptors ɑ2 Adrenergic receptors (inhibitory effect) ▫ Gq protein activation → second ▪ Presynaptic nerve terminals messenger cascade → ↑ phospholipase (autoreceptors) → presynaptic inhibition of C → ↑ IP3, DAG, Ca2+ → stimulatory neurotransmitter release effect ▪ Postganglionic parasympathetic nerve ▪ ɑ2 adrenergic receptors terminals in GI tract (heteroreceptors) → ↓ ▫ Gi protein activation → ↓ adenylate insulin secretion cyclase → ↓ cAMP → inhibitory effect ▪ ↓ platelet aggregation ▪ β1 adrenergic receptors β1 Adrenergic receptors (stimulatory ▫ Gs protein activation → ↑ adenylate cyclase → ↑ cAMP → stimulatory effect effect) ▪ β1 adrenergic receptors ▪ Heart ▫ Sinoatrial (SA) node → ↑ heart rate ▫ Gs protein activation → ↑ adenylate (positive chronotropic effect) cyclase → ↑ cAMP → stimulatory effect ▫ Atrioventricular (AV) node → ↑ conduction (positive dromotropic effect) CATECHOLAMINES ▫ Ventricular muscle → ↑ contractility ▪ Neurotransmitters synthesized, released by (positive inotropic effect) adrenergic neurons ▪ Salivary glands → ↓ salivation ▪ Include epinephrine (adrenaline), ▪ Adipose tissue → lipolysis norepinephrine (noradrenaline), dopamine ▪ Kidney → ↑ renin secretion 450 OSMOSIS.ORG  Chapter 51 Neurology: Autonomic Nervous System Synthesis ▪ Epinephrine ▪ Tyrosine → L-dopa; catalyzed by tyrosine ▫ MAO: dihydroxymandelic acid hydroxylase ▫ COMT: metanephrine ▪ L-dopa → dopamine; catalyzed by dopa ▫ Both: 3-methoxy-4-hydroxymandelic decarboxylase acid (VMA) ▪ Dopamine → norepinephrine; catalyzed by ▪ Dopamine β hydroxylase ▫ MAO: dihydroxyphenylacetic acid ▪ Norepinephrine → epinephrine; ▫ COMT: 3-methoxytyramine catalyzed by phenylethanolamine-N- ▫ Both: homovanillic acid (HVA) methyltransferase (PNMT); only in adrenal medulla Adrenergic transmission Degradation ▪ Present in ▪ All catecholamines can be degraded ▫ Most postganglionic sympathetic by deamination by monoamine oxidase neurons (norepinephrine) (MAO)/methylation by catechol-O- ▫ Adrenal medulla’s chromaffin cells methyltransferase (COMT)/both (epinephrine) ▪ Norepinephrine ▫ Ventral tegmental area, substantia nigra ▫ MAO: dihydroxymandelic acid (dopamine) ▫ COMT: normetanephrine ▫ Both: 3-methoxy-4-hydroxymandelic acid (VMA) Figure 51.6 Types of adrenergic receptors, the G-proteins with which they can be coupled, and the catecholamines that bind with them. OSMOSIS.ORG 451  CHOLINERGIC RECEPTORS osms.it/cholinergic-receptors ▪ Receptors respond to neurotransmitter ▪ Mechanism acetylcholine ▫ Acetylcholine binding → Gq (stimulatory) ▪ Located on parasympathetic effector or Gi (inhibitory) protein activation organs, CNS → stimulated → → second messenger cascade → ↑ parasympathetic/parasympathomimetic phospholipase C/↓ adenylate cyclase → response stimulatory/inhibitory effect ▫ M1, M3, M5 → Gq protein activation → ↑ Nicotinic receptors phospholipase C → ↑ IP3, DAG, Ca2+ → ▪ Ionotropic receptors stimulatory effect ▪ Type: location ▫ M4 → Gi protein activation → ↓ ▫ Nm: neuromuscular junction (non adenylate cyclase → ↓ cAMP → autonomic) inhibitory effect ▫ Nn: autonomic ganglia and adrenal ▫ M2 → Gi protein activation → K+ channel medulla activation → inhibitory effect ▪ Mechanism ▫ Acetylcholine binding → Na+, K+ ACETYLCHOLINE (ACh) diffusion → depolarization → voltage ▪ Neurotransmitter synthesized, released by Na+ channel activation → action cholinergic neurons potential → stimulatory effect ▪ Synthesis Muscarinic receptors ▫ Acetyl CoA + choline → acetylcholine; ▪ Metabotropic receptors (G-protein coupled catalyzed by choline acetyltransferase receptors) ▪ Degradation ▪ Located in CNS, all parasympathetic ▫ Acetylcholine → acetylcholine CoA + effector organs, some sympathetic effector choline; catalyzed by cholinesterase organs ▪ Cholinergic transmission is present in ▪ Type: location ▫ Basal ganglia, hippocampus, cerebral ▫ M1: autonomic ganglia, exocrine glands, cortex CNS ▫ All neuromuscular junctions ▫ M2: heart, sweat glands, CNS ▫ All preganglionic neurons (both ▫ M3: smooth muscle (blood vessels, parasympathetic, sympathetic neurons) lungs), glands, eyes, CNS ▫ All postganglionic parasympathetic ▫ M4: CNS, sweat glands neurons ▫ M5: CNS ▫ Some postganglionic sympathetic neurons (sweat glands) 452 OSMOSIS.ORG  Chapter 51 Neurology: Autonomic Nervous System Figure 51.7 Types of muscarinic receptors and the G-proteins with which they can be coupled. Figure 51.8 Mechanism of action of receptors coupled with Gq protein. The type of adrenergic receptor that couples with Gq protein is the alpha 1 receptor. The types of cholinergic muscarinic receptors that couple with Gq protein are the M1, M3, and M5 receptors. OSMOSIS.ORG 453  Figure 51.9 Mechanism of action of receptors coupled with Gs protein. The type of adrenergic receptor that couples with Gs protein is the beta receptor. The type of cholinergic muscarinic receptor that couples with Gs protein is the M3 receptor. Figure 51.10 Mechanism of action of receptors coupled with Gi protein. The type of adrenergic receptor that couples with Gi protein is the alpha 2 receptor. The types of cholinergic muscarinic receptors that couple with Gi protein are the M2 and M4 receptors. 454 OSMOSIS.ORG