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Neurotransmitter Receptor Dynamics: Ligands, Subtypes, and Effects

Explore the intricate world of neurotransmitter receptors, including ligand interactions, receptor subtypes, ionotropic vs. metabotropic receptors, and the diverse effects of neurotransmitters on neural signaling pathways. Dive into the mechanisms of action and potential drug implications.

catherinewhitmore
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Neurotransmitter Receptor Dynamics: Ligands, Subtypes, and Effects

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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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