Ervilla Dass Assistant Professor Department of Pharmacology S

Ervilla Dass Assistant Professor Department of Pharmacology S. B. K. S. Medical Institute and Research Centre Sumandeep Vidyapeeth, Piparia.

PARASYMPATHETIC NERVOUS SYSTEM Ervilla Dass

GENERAL ACTIONS OF ACETYLCHOLINE Promotes transmission in postganglionic autonomic fibers Promotes release of epinephrine and norepinephrine from the adrenal medulla Promotes transmission in skeletal muscle fibers Promotes the functions of the parasympathetic nervous system at cardiac muscle, smooth muscles and glands Promotes sympathetic thermoregulatory sweating

NEURONAL INNERVATION TO ORGANS

ACTIONS MEDIATED BY NN NICOTINIC RECEPTOR Autonomic ganglia Nicotinic sites Muscarinic sites Reproduced from Basic and Clinical Pharmacology • Adrenal medulla – Nicotinic sites: Release of epinephrine (90%) and norepinephrine (10%) into the circulation

ACTIVITIES WITHIN CELL BODIES OF AUTONOMIC GANGLIA POSTGANGLIONIC NEURON, SYMPATHETIC OR PARASYMPATHETIC

Actions Mediated by NM Nicotinic Receptor End plate of skeletal muscle fiber - generation of the EPP

NATURE OF NICOTINIC RECEPTORS • Nicotinic receptors are pentameric and ionotropic - the receptor proteins themselves form ion channels • The ion channels are ligand-gated • Two subtypes – NN subtype is present on cell body of postganglionic autonomic neuron – NM subtype is present at the endplate of the neuromuscular junction

AGONISTS AND ANTAGONISTS AT NICOTINIC RECEPTOR SUBTYPES

RESPONSE TO DOSES OF NICOTINE Low Dose Autonomic ganglia Adrenal medullary cell End plate of skeletal muscle High Dose Autonomic ganglia Adrenal medullary cell End plate of skeletal muscle

MUSCARINIC RECEPTORS Muscarinic receptors The alkaloid muscarine mimics the actions of acetylcholine at these receptor sites Metabotropic �Associated with guanine nucleotide binding proteins (G- proteins) �Span the cell membrane seven times Several subtypes: M 1, M 2, M 3, M 4, M 5 Associated with various biochemical and electrophysiological responses

BIOCHEMICAL ACTIONS ASSOCIATED WITH MUSCARINIC RECEPTORS M 2, and M 4 muscarinic receptors associate with Gi-protein; result: inhibition of adenyl cyclase X M 1, M 3, and M 5 muscarinic receptors associate with Gq-protein; result: activation of phospholipase Cb phosphatidylinositolbiphosphate (PIP)2 inositoltriphosphate (IP)3 diacylglycerol (DAG)

SPECIFIC ANTAGONISTS FOR MUSCARINIC RECEPTOR SUBTYPES RECEPTOR M 1 M 2 M 3 TISSUE SELECTIVE ANTAGONIST(S) Autonomic ganglia, gastric tissue Cardiac muscle fiber Pirenzepine Telenzepine Smooth muscles and glands Darifenacin *Also blocks the nicotinic receptor Tripitamine Gallamine*

EVIDENCE

K. D. Tripathi M. D. , Essentials of Medical Pharmacology , 7 th dition , 2013, pg. 99 to 102 Source of Information Chapter Author Information Level of evidence K. D. Tripathi Essentials of Medical Pharmacolog y, Jaypee Brothers Medical Publishers (P) LTD, NEW DELHI Section II DRUGS ACTING ON AUTONOMI C NERVOUS SYSTEM Dr. K. D. Tripathi M. D. Ex-Director Professor and head of Pharmacolog y Maulana Azad Medical College and Associated LN B Pant Hospitals, New Delhi Cholinergic receptors, location action Level of evidence Grade one 7 th edition, 2013 Chapter 7 cholinergic system and drugs

Satoskar & Bhandarkar, Pharmacology and Pharmacotherapeutics , Revised 23 rd Edition , 2013, pg. 286 to 289 Source of Information Chapter Pharmacolog y and Pharmacothe rapeutics – R. S. Satoskar, S. D. Bhandarkar, Nirmala N. Rege POPULAR PRAKASHA N, Mumbai. Section IV Satoskar & AUTONOMI Bhandarkar C NERVOUS SYSTEM Revised 23 rd Edition, 2013 Chapter 18 Cholinergic drugs Author Information Level of evidence Cholinergic receptors, location action Level of evidence Grade one

Source of Information Chapter Author Information 1. Eur J Neurosci. 2010 Mar; 31(6): 97893. doi: 10. 1111/j. 1460 9568. 2010. 071 33. x. Epub 2010 Mar 3. Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of n. ACh. R subunit genes. David R 1, Ciuraszkiewicz A, Simeone X, Orr-Urtreger A, Papke RL, Mc. Intosh JM, Huck S, Scholze P. Acetylcholine Nicotinic acetylcholine receptors (n. ACh. Rs) mediate fast synaptic transmission in ganglia of the autonomic nervous system. Level of evidence

Source of Information Chapter Author Information 1. Eur J Neurosci. 2010 Mar; 31(6): 97893. doi: 10. 1111/j. 1460 9568. 2010. 071 33. x. Epub 2010 Mar 3. Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of n. ACh. R subunit genes. David R 1, Ciuraszkiewicz A, Simeone X, Orr-Urtreger A, Papke RL, Mc. Intosh JM, Huck S, Scholze P. Acetylcholine Nicotinic acetylcholine receptors (n. ACh. Rs) mediate fast synaptic transmission in ganglia of the autonomic nervous system. Level of evidence

Source of Information Chapter Author Information Acta Physiol (Oxf). 2013 Jan; 207(1): 1633. doi: 10. 1111/apha. 12010. Epub 2012 Oct 15. Autonomic nervous control of the urinary bladder. Ochodnicky Acetylcholine P 1, Uvelius B, Andersson KE, The Michel MC. autonomic nervous system plays an important role in the regulation of the urinary bladder function. interactions between the adrenergic and cholinergic system, which have been studied Level of evidence