Acetylcholine Other Neurotransmitters Lesson 10 Acetylcholine ACh Peripheral

Acetylcholine & Other Neurotransmitters Lesson 10

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

Acetylcholine - ACh Receptor subtypes: 2 major groups n Nicotinic receptors - ionotropic l excitatory n Muscarinic receptors - metabotropic l excitatory or inhibitory n Degraded by acetylcholinesterasen l ACh. E l Membrane bound upre- & postsynaptic membrane -~

ACh Synthesis choline acetyltransferase choline + acetyl Co. A ACh

Cholinergic Agonists n Direct l Muscarine l Nicotine usmall doses ~

ACh. E inhibitors Physostigmine n Organophosphates - irreversible l DFP l Soman & Sarin l Malathion n Agonist or Antagonist? indirect agonist ~ n

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

ACh Botulinus toxin BWSV ACh. E N M curare atropine ACh. E

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

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

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

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

GABA Synthesis glutaminase Glutamine glutamate decarboxylase Glutamate GABA

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

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

Endorphins n Opioids u. Dynorphin umet-enkephalin uleu-enkephalin u. Beta-endorphin n Receptor subtypes: l m 1, m 2, k, d ~

Endorphins n Agonists morphine u heroin u codeine u n Antagonists l naloxone l naltrexone ~

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

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

Focus on ACh NE DA 5 HT GABA Endorphins