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Neurotransmitters & Receptors

Neurotransmitters & Receptors. Lecture 10. Ligands & Receptors. Ligand Neurotransmitters (NT) & Drugs Receptor proteins Control ion channels NT binds to receptor Activation EPSP or IPSP Receptor subtypes ~. Lock & Key Model. NT binds to receptor NT = key Receptor = lock

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Neurotransmitters & Receptors

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  1. Neurotransmitters & Receptors Lecture 10

  2. Ligands & Receptors • Ligand • Neurotransmitters (NT) & Drugs • Receptor proteins • Control ion channels • NT binds to receptor • Activation • EPSP or IPSP • Receptor subtypes ~

  3. Lock & Key Model • NT binds to receptor • NT = key • Receptor = lock • Affinity (attraction) • Binding site • Physical fit • Electrical fit ~

  4. Receptor A Receptor B • Same NT can bind to different -R • different part of NT ~ NT

  5. Receptor Subtypes • Same NT • Binds to many receptor subtypes • Produce different effects • EPSP or IPSP • All NT systems • Several subtypes each • Drug side effects ~

  6. Ionotropic receptors • Ligand-gated channels • Ion channels • NT directly controls channel • fast action • transient ~

  7. Metabotropic receptors • Requires energy • GTP • Receptor indirectly controls channel • G protein-gated ion channels • 2d messenger systems • neuromodulation • slower action • changes in sensitivity of neuron ~

  8. 2d Messenger Systems • Effects relatively slow • Signal amplification • 1 NE  activate adenlyl cyclase  • ATP 1000s cAMP  10,000s  • cAMP  10,000s phosphates • Effects • Control channel • Alter properties of receptors • regulation of gene expression ~

  9. A C R G GTP G protein: Protein Phosphorylation ATP cAMP P PKA

  10. A C R G GTP Pore G protein: Protein Phosphorylation ATP P cAMP PKA

  11. Neurotransmitters • Chemical messengers • Signal between cells • Acetylcholine (ACh) • Monoamines • Amino Acids • Peptides • Purines & Gases ~

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

  13. Acetylcholine - ACh • Receptor subtypes: 2 major groups • Nicotinic receptors - ionotropic • excitatory • Muscarinic receptors - metabotropic • excitatory or inhibitory • Degraded by acetylcholinesterase- • AChE ~

  14. Monoamines • 2 groups • Amino acid precursors • Catecholamines - tyrosine • Indolamine - tryptophan • Affected by many of same drugs ~

  15. Catecholamines Dopamine - DA Dopaminergic Norepinephrine - NE Noradrenergic Epinephrine - E Adrenergic ~ Indolamines Serotonin - 5HT Serotonergic Monoamines

  16. Monoamines • Terminated by... • reuptake • MAO - monoamine oxidase • COMT - catechol-O-methyltransferase • also in liver • Reserpine  blocks storage • initially stimulates NT release • profound depletion over several days ~

  17. Amino Acids • GABA • Gamma-amino-butyric acid • Inhibitory • CNS • Glutamate • Excitatory • CNS ~

  18. Other Neurotransmitters • Peptides • Amino acid chains • Substance P • Endorphins • Purines • ATP • Nitric Oxide (NO) • Poisonous gas? • Carbon monoxide? • Anandamide • At THC receptors • Many others ~

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