BIOL2048-49 ANS Lecture 4 DGN 24-25 PDF

Topics: Transmission at the post-ganglionic sympathetic synapse 1. synthesis, release, uptake and metabolism of noradrenaline 2. classification and pharmacology of noradrenaline receptors 3. drugs that interfere with post-ganglionic sympathetic transmission Tra...

Topics: Transmission at the post-ganglionic sympathetic synapse 1. synthesis, release, uptake and metabolism of noradrenaline 2. classification and pharmacology of noradrenaline receptors 3. drugs that interfere with post-ganglionic sympathetic transmission Transmission at cholinergic synapses in the autonomic nervous system 4. synthesis and release of acetylcholine 5. ganglionic neurotransmission, nicotinic receptors 6. post-ganglionic neurotransmission, muscarinic  Dale's experiment showing that ACh produces 2 different effects on blood pressure BP atropine 2µg 50µg 50µg5mg ACh injected IV with bradycardia MUSCARINIC tachycardia NICOTINIC Why the same compound triggers two dose- dependent opposite responses?  Parasympathetic Organ Synapse Acetylcholinesterase Ca 2+ Effector Organ Na+ K+ G Action Potential ACH Muscarinic Receptor Postganglionic neuron  Muscarinic receptor subtypes: overview All are G protein coupled receptors M1 M2 M3 Type neural cardiac glandular main location CNS atria exocrine glands, presynaptic smooth muscle, terminals vascular endothelium cellular action ↑IP3, DAG ↓cAMP ↑IP3, DAG function gastric acid cardiac inhibition secretion secretion neural inhibition smooth muscle gut motility contraction vasodilation (via NO)  Muscarinic receptor subtypes: overview M1 M2 M3 Type neural cardiac glandular Function -gastric acid -cardiac -secretion secretion inhibition -smooth muscle -gut motility -neural inhibition contraction -vasodilation (via NO) Muscarinic receptor antagonists atropine pirenzepine Effects of muscarinic antagonists inhibition of secretions effect on heart rate effects on the eye effects on the gut effects on other smooth muscle effects on the CNS CLINICAL USES Nicotinic transmission at autonomic ganglia (Para)sympathetic Ganglionic Synapse Ca 2+ Acetylcholinesterase Na+ ACH aba Action Potential Nicotinic Receptor Na + Preganglionic neuron Postganglionic neuron  Nicotinic receptors all are ligand-gated ion channels and are permeable to cations e isoform at ganglia is different from the mus  Nicotinic receptor agonists acetylcholine nicotine Effect of nicotine: stimulation of autonomic ganglia  Nicotinic receptor agonists acetylcholine dimethylphenylpiperazinium Effects of DMPP: stimulation of autonomic Nicotinic ganglionic receptor antagonists hexamethonium amethonium blocks ganglionic nicotinic recep shown in the cat nictitating membrane preparation by Paton and Zaimis, 1949. what does this experiment tell you about the action of hexamethonium? he pharmacological actions of hexamethonium blocks the nicotinic receptor- no agonist action reduces blood pressure (beneficial in hypertension) but also causes dry mouth, reduced gastric acid secretion, constipation, urinary retention, blurred vision, postural hypotension and sexual dysfunction Hex belongs to a series of compounds hexamethonium polymethylene bismethonium series decamethonium Paton & Zaimis compared the effect of polybismethonium compounds at autonomic ganglia and neuromuscular junction here 'n' is the number of carbons in the chain =6 is hexamethonium n=10 is decamethonium  Summar y Here we have discussed the role of nicotinic transmission at the autonomic ganglia (we have not covered the role of other neurotransmitters which are involved primarily in modulation of signalling) You should be able to compare the pharmacological actions of drugs that act at the autonomic ganglia or the skeletal neuromuscular junction  LEARNING OUTCOMES You should be able to: 1. Outline the actions of drugs which interact with the sympathetic nervous system with reference to autonomic processes such as control of blood pressure 2. Describe the mechanisms of action of drugs which interact with the parasympathetic nervous system and their sites of action