Lecture 6 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (firstname.lastname@example.org) at Willamette University. Includes neurotransmitter release, reuptake, and inactivation
Text of Neuropharmacology: Neurotransmission
1. Neurocommunication Brian J. Piper, Ph.D.
2. Terminology Neurotransmitter: chemical that is released inthe brain and has an effect on a local target Hormone: chemical that is released intobloodstream that has an effect on a distanttarget 3. Goals Neurotransmission History Onset: Neurotransmitter release (classical andnon-classical) Offset: autoreceptors, transporters, enzymes Receptor Families Endocrine 4. History: Golgi vs. Cajal Italian physician Reticulum theory Silver stainCamillo Golgi (1843-1926) 5. Controversy: Golgi vs. Cajal Santiogo Ramon y Cajal Neuroanatomist Used Golgis technique Neuron theory1852-1934Chicken cerebellum 6. Neural Communication The bodys information system is built frombillions of interconnected cells called neurons. Communication between neurons is both electrical and chemical. 7. Otto Loewi Discovered Vagusstoff laterknown as acetylcholine father of neuroscience Nobel Prize 1936 8. What are amino acids? Amine (NH2) + Carboxyl ( -COOH) 20 total, 9 essentialtyrosineTryptophan 9. More terminology Peptides: short ( AB Enzyme: CD__ENZ____> C + D 26. Transporters Proteins that move molecule from one placeto another, examples: SERT: serotonin transporter NET: norepinephrine transporter DAT: dopamine transporterInside----------------------------------------------------------------------Outside 27. Post-synaptic Ligand: substance that binds to a receptor Ion: atom where # electrons # protons Ca2+ Na+ K+ Cl- First messenger: neurotransmitter Second messenger: other molecule Kinase: enzyme that adds phosphate (PO4) 28. Types of Receptors 29. So Many Receptors! Serotonin (5-HT): 1 2 3 4 5 6 7 30. Family 1: Ionotropic Binding to receptor opens channel to let ionsin (aka: ligand gated ion receptors) 31. Family 1: Ionotropic Binding to receptor opens channel to let ionsin (aka: ligand gated ion receptors)0:40 6:20: http://www.youtube.com/watch?v=8jPH2pKzIDY 32. Family 2: Metabotropic (2nd messenger) Steps: 1) Ligand binds receptor 2) G protein acts on enzyme 3) Enzyme regulates 2ndmessenger 4) 2nd messenger acts onprotein kinase6:30-9:00 http://www.youtube.com/watch?v=8jPH2pKzIDY 33. Family 2: Metabotropic (Channel) Steps: 1) Ligand binds receptor 2) G protein alterschannel 3) ions flow out of neuron 34. Receptor Families Compared Ionotropic MetabotropicSubunits 4-51MechanismSimple: Channel openingComplex: G protein cascade2nd messengers No YesSpeedFast Slow Meyer & Quenzer (2005). p 73 35. Family 3: Tyrosine Kinase Steps:1) Ligand (BDNF) binds to Trk receptor2) Trk receptors come together, andphosphorylate each other 36. So many drug targets!!!Examples:1) Tryptophan6) Nicotine10) MAO-I11) SSRIs 37. Endocrine SystemGlandHormone (Function)Pineal Melatonin (light-dark rhythm)ThyroidT3/T4 (energy)AdrenalCortisol (stress)Pancreas Insulin (glucose)OvariesEstrogens (2nd sex characteristics)Testes Androgens (2nd sex characteristics) 38. Example Rats that received ecstasy (MDMA) duringadolescence were more sensitive to a 5-HT2agonist when adultsBiezonski et al. (2009). Brain Research, 1252, 87-93. 39. Reference