Acetylcholine & Other Neurotransmitters Lesson 10

Acetylcholine - ACh Peripheral N.S. Skeletal muscle contraction Autonomic NS Ganglia Parasympathetic neuroeffector junction Central N.S. - widespread Hippocampus Hypothalamus ~

Acetylcholine - ACh AChE Receptor subtypes: 2 major groups Nicotinic receptors - ionotropic excitatory Muscarinic receptors - metabotropic excitatory or inhibitory Degraded by acetylcholinesterase- AChE Membrane bound - pre- & postsynaptic membrane -~

ACh Synthesis choline acetyltransferase choline + acetyl CoA ACh

Cholinergic Agonists Direct Muscarine Nicotine small doses ~

AChE inhibitors Physostigmine Organophosphates - irreversible DFP Soman & Sarin Malathion Agonist or Antagonist? indirect agonist ~

Cholinergic Antagonists Direct Nicotinic - Curare Muscarinic - Atropine Scopolamine Indirect Hemicholinium Botulinus Toxin Black Widow Spider Venom ~

ACh Botulinus toxin BWSV AChE N M curare atropine

Excitatory Amino Acids: Glutamate Primary NT in CNS excitatory neurons Nonessential amino acids Synthesis Precursor glutamine from astroglia Termination presynaptic & glial reuptake ~

Excitatory Amino Acids: Glutamate Receptor subtypes Metabotropic (mGlu-R) Inhibition of Na+ & Ca++ channels Iononotropic: NMDA-R; AMPA-R nonselective Excitotoxicity Following brain injury Elevated Glu activity Aspartate ~

Inhibitory Amino Acids: Glycine Primarily spinal cord Cl- channels Strychnine is antagonist ~

Inhibitory Amino Acids: GABA GABA - GABAergic Major NT in brain inhibitory system Receptor subtypes GABAA - controls Cl- channel GABAB - controls K+ channel Degradation by GABA-T GABA aminotransferase ~

GABA Synthesis Glutamine Glutamate GABA glutamate decarboxylase glutaminase Glutamine Glutamate GABA

GABAergic Drugs ß CCM ~ Ro 15-4513 Agonists Antagonists Benzodiazepines Barbiturates Ethyl alcohol (ETOH) Antagonists Picrotoxin Inverse agonist Ro 15-4513 ß CCM ~

Neuropeptides Chains of amino acids Synthesis in soma Often neuromodulators Substance P - pain Endorphins - analgesia, euphoria ~

Endorphins m1, m2, k, d ~ Opioids Receptor subtypes: Dynorphin met-enkephalin leu-enkephalin Beta-endorphin Receptor subtypes: m1, m2, k, d ~ Methionine & Leucine

Endorphins Agonists Antagonists naloxone naltrexone ~ morphine heroin codeine Antagonists naloxone naltrexone ~

Some Other NTs Histamine Inflammatory Response Nitric Oxide - It’s a gas Retrograde messenger Ca++-dependent Not stored in vesicles ~

Some Other NTs Endocannabinoids Anandamide 2 - AG Inhibits presynaptic GABA release Synthesis by enzymatic degradation of membrane ~

Focus on ACh NE DA 5HT GABA Endorphins