Autonomic Nervous System Physiology PDF

The physiology of the Autonomic Nervous System The functional role of cholinergic and adrenergic receptors in the autonomic nervous system 1st Medical year / Lecture (5) 2024/2025  Cholinergic Receptors...

The physiology of the Autonomic Nervous System The functional role of cholinergic and adrenergic receptors in the autonomic nervous system 1st Medical year / Lecture (5) 2024/2025  Cholinergic Receptors classification Nicotinic R Muscarinic R nAChRs mAChRs Response to ACh & Nicotine Response to ACh & Muscarine Ionotropic ligand-gated receptors G protein-coupled receptors NnR NmR Autonomic ganglia M1 - M2- M3 - M4 - M5 Skeletal muscles CNS ⊕ ⊖ ⊕ ⊖ ⊕ (NMJ)  Cholinergic Receptors AG M1,2&3 NnR ACh ACh Cholinergic fibers Cholinergic fibers ALL Sympathetic or ALL parasympathetic parasympathetic and some sympathetic Effector Preganglionic neuron postganglionic neuron  Cholinergic Receptors Cholinergic receptors function in signal transduction of the somatic and autonomic nervous systems. The receptors are named because they become activated by the ligand acetylcholine. These receptors subdivide into nicotinic and muscarinic receptors, which are named secondary to separate activating ligands that contributed to their study. Nicotinic receptors are responsive to the agonist nicotine, while muscarinic receptors are responsive to muscarine. The two receptors differ in function as ionotropic ligand-gated and G-protein coupled receptors, respectively. Nicotinic receptors function within the central nervous system, autonomic ganglia and at the neuromuscular junction. While muscarinic receptors function in both the peripheral and central nervous systems, mediating innervation to visceral organs. The difference in signal transduction of the two receptor types confers separate physiological functions upon receptor activation. Differences in receptor subtypes create unique implications for pharmacologic targets and pathogenesis of the disease.  Nicotinic R nAChRs ACh  Muscarinic R G protein-coupled receptors ⊕ Gq M1 - M2- M3 - M4 - M5 ⊖ Gi ⊕ ⊖ ⊕ ⊖ ⊕  Effect on the Eye Ciliary muscle CONTRACTED Sphincter pupillae muscle ➔ CONTRACTION  Effect on the heart M2 HEART Reduce heart rate (Bradycardia) ➔depolarization Reduce contractile forces of the atrial cardiac muscle Slow conduction velocity of AV node  Adrenergic Receptors classification α1 α2 β1 β2 β3 High-affinity➔ Noradrenaline High-affinity➔ adrenaline Response to Catecholamines G protein-coupled receptors  Adrenergic Receptors Adrenergic receptors are the receptors that bind and respond to noradrenaline (norepinephrine) and adrenaline (epinephrine). Catecholamines (noradrenaline and adrenaline) are involved in the stimulation of body organs by the sympathetic nervous system; they help to trigger the fight or flight response These receptors are G protein-coupled receptors mainly involved with the sympathetic nervous system. The classification of these receptors is based on the interaction of agonists and antagonists with the receptors. There are two adrenergic receptors namely α-receptors (Alpha 1 and 2) & β-receptors (beta 1, 2 and 3). Beta 2 receptors have a higher affinity towards adrenaline while alpha receptors show a higher affinity towards noradrenaline. Among these receptors, α1 & β1 are responsible for excitation while α2 & β2 are responsible for inhibition. cAMP cAMP IP3/DAG (Ca2+)  Effect of adrenergic receptors α1 α2 β1 β2 β3 Vasoconstriction Vasodilatation (  peripheral resistance)  Norepinephrine  Hear rate Bronchodilatation  Lipolysis Mydriasis release  Myocardial  Glycogenolysis piloerector muscle  Insulin release contractility Urinary bladder contraction  Renin relaxation GIT and urinary Uterine relaxation sphincters contraction All tissues to be stimulated should have α1R except : All tissues to be inhibited should have β2R except : 1. HEART→β1 1. Presynaptic adrenergic nerve endings →α2 2. Juxtaglomerular apparatus→ β1 2. Beta cells of pancreas→ α2 3. Metabolism ( Glycogenolysis →β2) & (Lipolysis →β3 ) 3. Platelets & some parts of GIT  Effect on the Respiratory system α1 blood vessels β2 smooth muscles  Effect on Cardiovascular system β2 α1 Autoregulation β2 α1 α1  Effect on the heart β1 Β1 receptor increases sinoatrial (SA) nodal, atrioventricular (AV) nodal, and ventricular muscular firing, thus increasing heart rate and contractility. With these two increased values, the stroke volume and cardiac output will also increase.  Effect on GIT sphincters and muscles β2 Glycogenolysis β2 α1 GIT sphincters α1 GIT smooth muscles β2 Glycogenolysis β2 Insulin secretion α2 α1  Effect on the kidney, urinary bladder, and uterus β2 α1 α1 β2 β1 In the kidney, smooth muscle cells in the juxtaglomerular apparatus contract and release renin. This cascading effect will eventually increase blood volume through the actions of angiotensin II and aldosterone.  Effect on the Eye α1 β2 Ciliary muscle RELAXED Dilator pupillae muscle➔ CONTRACTION  Presynaptic receptors They are present in the membranes of postganglionic adrenergic nerve endings. NE They are auto-receptors that regulate the release of chemical transmitters from the postganglionic adrenergic nerve endings Target nerve endings. Stimulation of the alpha 2 presynaptic receptors decreases the release of noradrenaline by negative feedback