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ANS Review ANS maintains you & allows you to respond to the environment SYMPATHETIC • Mobilizes body to expend energy • Targets widely distributed organ systems Blood vessels, sweat glands, piloerector muscles FEAR Sympathetic & adrenal medulla: Fight or flight response mobilizes the body to expend energy for extreme sustained physical exertion . • Cardiovascular System – Increase in heart rate & force of contraction increased cardiac output (5L/min 25-40L/min) – Increase in BP – Redistribution of blood flow • Respiratory System – Airways are dilated • Digestive System – GI function (motility and secretions) inhibited • Metabolism – Glucose is mobilized – Lipolysis is stimulated – Metabolic rate increases Stimuli that release adrenal medullary catecholamines • Physiological stressors – Psychological: emotional states - fear – Metabolic – Hypothermia • Pathological stressors – Severe hemorrhage – Heart attack – Pain NOTE: Asthmatic attacks do not release CAs ANS maintains you & allows you to respond to the environment SYMPATHETIC • Mobilizes body to expend energy • Targets widely distributed organ systems PARASYMPATHETIC • Restorative role; conserves energy • Discrete targeted control General feature of ANS • Tonically active system • Always have basal level of end organ activity • Often modulates ongoing spontaneously generated activity (heart; GI tract) • Activity controlled reflexly & most autonomic reflexes are readily affected by emotional state post pre Parasympathetic Cranial Spinal cord T1 pre post Sympathetic Thoraco-lumbar pre Collateral ganglia Adrenal Splanchnic nerve L3 pre Parasympathetic Sacral post S2 S3 S4 Schematic ANS: Organization 1:1/1:2 pre Parasympathetic Cranial Spinal cord T1 Targeted control Divergence/convergence Diffuse targets Sympathetic pre Collateral ganglia Adrenal Splanchnic nerve L3 pre S2 S3 S4 Parasympathetic Sacral 1:1/1:2 Targeted control Schematic ANS: Wiring of ganglia Neuroeffector junction: Sympathetic postganglionic nerve terminal is a diffusely distributed complex branching network with varicosities (swellings) Synaptic vesicle ANS TRANSMITTERS Ach Ach Spinal cord T1 Sympathetic postganglionics to sweat glands Ach Ach Ach Adrenal Biological inactivation: Breakdown: acetylcholinesterase Resupply: De novo synthesis in terminal L3 Ach S2 S3 S4 Ach • All preganglionic neurons release Ach • All postganglionic parasympathetic neurons release Ach • Sympathetic postganglionics general sweat glands (except sweat gland on palms, soles of feet, & underarms) release Ach ANS TRANSMITTERS Ach Ach Spinal cord T1 Ach NE Ach NE EPI – 80% Adrenal L3 Biological inactivation of NE: REUPTAKE Resupply of NE: recycling & new synthesis Ach S2 S3 S4 Ach Sympathetic postganglionic neurons release NE (except to generalized sweat glands; Adrenal medulla releases NE and EPI (80%) Peptides also in LDCV in terminals along with Ach & NE Peptides • Stored in LDCV • Never located at plasma membrane • Released only by high frequency stimulation • Peptides augment actions of low molecular weight transmitter (ACh or NE) • Biological inactivation: breakdown by peptidases ANS RECEPTORS – ganglion - nicotinic Ach Ach nicotinic Spinal cord nicotinic T1 Ach NE Ach nicotinic L3 Differences between ganglionic & skeletal NMJ nicotinic receptors: • Subunit composition • Sensitivity to antagonists Ach S2 S3 S4 Ach nicotinic Somatic motor nerve All postganglionic neurons, cells of the adrenal medulla & skeletal NMJ have nicotinic cholinergic receptors Skeletal NMJ ANS RECEPTORS Ach Ach (+) (-) Spinal cord muscarinic T1 Ach Sweat gl. (+) Sympathetic postganglionics to generalized sweat glands release Ach Ach muscarinic L3 Ach S2 S3 S4 Ach (+) Cholinergic receptors of the muscarinic type are on effector tissues innervated by parasympathetic postganglionic neurons and on generalized sweat glands ANS RECEPTORS -Adrenergic post pre Parasympathetic Cranial Spinal cord T1 pre NE post Sympathetic pre Adrenal Splanchnic nerve L3 pre EPI NE Parasympathetic Sacral Alpha-1 & 2 Beta-1 & 2 post S2 S3 S4 Schematic ANS Receptors for NE Alpha-1 receptors • Excitatory contraction of smooth muscle • Most important location -- smooth muscle of blood vessels • Insensitive - require high concentrations of agonist; NE & EPI ~ equipotent • Under physiological conditions, a-1 receptors are activated by NE released from sympathetic nerves. • EPI released from adrenal in response to stress never reaches high enough concentrations in the circulation to activate a-1 receptors • Effects mediated by IP3 production Receptors for NE Alpha-2 receptors are presynaptic • Inhibitory receptors located on nerve terminals. – Autoreceptors on sympathetic postganglionic terminals; – Hetero-receptors on terminals of parasympathetic nerves of the GI tract bind NE, released from adjacent postganglionic sympathetic nerves. – Activation of a-2 receptor reduces evoked transmitter release by reducing Ca2+ entry into presynaptic terminal a-2 heteroreceptors mediate sympathetic inhibition of GI tract BETA-1 RECEPTORS • Excitatory response to both NE & EPI • Location – heart: beats faster and more strongly • Beta-1 receptor is very sensitive to both NE & EPI – so heart can be stimulated by NE released from sympathetic nerves or EPI released from the adrenal medulla • Beta-1 effects mediated by stimulation of cAMP production BETA-2 RECEPTORS • inhibitory relaxation of smooth muscle • very sensitive to EPI, but not NE • activated in response to stress (when adrenal medulla secretes EPI into the circulation) • found on smooth muscle of airways, GI tract, & blood vessels supplying skeletal muscle (along with alpha-1 receptors) – Beta-2 agonists used for acute treatment of asthmatic attacks • stimulate production of cAMP Blood vessels of skeletal muscle Transmitter Receptor Action Target ACh nicotinic +++ Postganglionic Ligand neurons gated ion channel depolarization ACh muscarinic +++ Smooth m Glands Heart GPCR IP3 induced Ca release Opens K+ channel Smooth m Glands Nerve varicosities GPCR --- Signalling Mechanism GPCR Action a-1 +++ a-2 ---- NE EPI b-1 +++ Heart GPCR cAMP EPI b-2 ---- Smooth m GPCR cAMP NE GPCR IP3 induced Ca release Ca entry Examples of ANS Reflexes • Pupillary light reflex • Stress activation of the adrenal medulla • Reflex regulation of the GI tract (CNS & LOCAL) – Parasympathetic Nervous System • Vago-vagal activation of stomach (CNS) • Gastro-colic reflex (CNS) – Enteric Nervous System - Locally mediated stereotyped movements (e.g. peristalsis) – Sympathetic Nervous System • Global inhibition (stress response - CNS) • Enterogastric reflex: selective local inhibition: • Tonic inhibition (local) ENS PARASYMPATHETIC SYMPATHETIC