1 / 46

Chemical Messengers

Chemical Messengers. Autocrine self signal Paracrine neighbor signal Endocrine distant signal Pheromone airborne signal same species Allomone airborne signal different species. Endocrine Glands. Homeostasis Mechanism. Receptors input signals skin responds to cold temperature

jeank
Download Presentation

Chemical Messengers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chemical Messengers • Autocrine • self signal • Paracrine • neighbor signal • Endocrine • distant signal • Pheromone • airborne signal • same species • Allomone • airborne signal • different species

  2. Endocrine Glands

  3. Homeostasis Mechanism Receptors input signals skin responds to cold temperature sends signal to brain Control Center integrating center brain interprets temp signal makes you shiver Effectors output mechanism muscles shiver creating heat

  4. Neurotransmitters • Neuropeptides • Opioid peptides • Enkephalins (ENK) • Endorphins (END) • Peptide Hormones • Oxytocin (Oxy) • Substance P • Cholecystokinin (CCK) • Vasopressin (ADH) • Neuropeptide Y (NPY) • Brain-derived Neurotrophic factor • Hypothalamic Releasing Hormones • GnRH • TRH • CRH • Lipids • Anandamide • Gases • Nitric Oxide (NO) • Amines • Quaternary amines • Acetylcholine (ACh) • Monoamines • Catecholamines • Epinephrine (EPI) • Norepinephrine (NE) • Dopamine (DA) • Indoleamines • Serotonin (5-HT) • Melatonin • Amino acids • Gamma-aminobutyric acid (GABA) • Glutamate (GLU) • Glycine • Histamine (HIST)

  5. Acetylcholine Synthesis Breakdown

  6. Cholinergic Synapse • Choline • Acetyl CoA • Cholinesterase (ChAT) • Acetylcholinesterase (AChE) • Choline transporter • Vesicular ACh transporter (VAChT)

  7. Cholinergic (Ach) System

  8. Nicotinic receptors • Muscle Type • Neuromuscular junction • Autonomic ganglia • CNS Type • Muscarinic receptors • M1 • CNS • Autonomic ganglia • M2 • Heart • M3 • Blood vessels • Lungs • Exocrine Glands • M4 • CNS • M5 • CNS Cholinergic Receptors Iontotropic metabotropic Nicotinic ACh Receptor

  9. Catecholamine Synthesis

  10. Noradrenergic (NE) System

  11. Noradrenergic Receptors • Alpha 1 receptors • Smooth muscle • Skin • GI tract • Kidney • brain • Alpha 2 receptors • brain • Beta 1 receptors • Heart • kidneys • Beta 2 receptors • Lungs • GI tract • Liver • uterus • Vascular smooth muscle • Skeletal muscle • Beta 3 receptors • Fat cells All metabotropic

  12. Dopaminergic Synapse • Tyrosine • Tyrosine Hydroxylase • DOPA • Aromatic Amino Acid Decarboxylase • Dopamine Transporter • Vesicular Monoamine Transporter • D2 Autoreceptor

  13. Dopaminergic (DA) System 1Mesolimbic * Ventral Tegmental Area (VTA)

  14. Dopaminergic (DA) System 2Mesostriatal * Basal Ganglia

  15. Dopaminergic Receptors • D1 receptors • D2 receptors • D3 receptors • D4 receptors • D5 receptors

  16. Serotonin(5-Hydroxytryptamine)(5-HT)

  17. Serotonergic Synapse • Tryptophan • Tryptophan hydroxylase • 5-HTP • Aromatic l-amino acid decarboxylase (AADC) • 5-HT • 5-HT transporter • 5-HT autoreceptor

  18. Serotoninergic (5-HT) System

  19. 5-HT1A-F receptors • CNS • Blood Vessels • 5-HT2A-C receptors • CNS • PNS • Blood Vessels • GI Tract • 5-HT3 receptors • CNS • PNS • GI Tract • 5-HT4 receptors • CNS • PNS • GI Tract • 5-HT5A-B receptors • CNS • 5-HT6 receptors • CNS • 5-HT7 receptors • CNS • Blood Vessels • GI Tract Serotonergic Receptors • Iontotropic • Metabotropic 5-HT1B receptor

  20. Glutamate Synthesis • Glutamine • Glutaminase • Glutamic Acid • Glutamate • Aspartic Acid • Aspartate

  21. Glutamate Synapse

  22. Glutamate Receptors • AMPA receptors • GluA1-4 • Kainate receptors • GluK1-5 • NMDA receptors • GluN1 • GluN2A-C • GluN3A-B • Metabotropic receptors • mGluR1-8 Iontotropic Metabotropic AMPA Receptor

  23. Long-Term Potentiation (LTP) each triangle represents a single action potential Slope of the EPSP (one characteristic measure of an action potential) baseline response potentiated response Hippocampus has a three synaptic pathway Stimulate one area (mossy fibers) and record the action potentials in another (CA1) Stimulate multiple times to get a baseline response Once a stable baseline is established give a brief high frequency stimulating pulse Use the same stimulating pulse as in baseline but now see a potentiated response This potentiated response can last hours, days, or even weeks (LTP)

  24. Normal Synaptic Transmission Glutamate Channels: NMDA Mg2+ block no ion flow AMPA Na+ flows in depolarizes cell

  25. LTP Induction With repeated activation the depolarization drives the Mg2+ plug out of the NMDA channels Ca2+ then rushes in through the NMDA channels Ca2+ stimulates a retrograde messenger to maintain LTP Ca2+ also stimulates CREB to activate plasticity genes

  26. LTP-induced Neural Changes

  27. Neurobiological Changes via Learning Dendritic changes: • Increased dendritic arborization • Increased dendritic bulbs Synaptic changes: • More neurotransmitter release • More sensitive postsynaptic area • Larger presynaptic areas • Larger postsynaptic areas • Increased interneuron modulation • More synapses formed • Increased shifts in synaptic input Physiological changes: • Long-Term Potentiation • Long-Term Depression

  28. GABA Synthesis • Glutamate • Glutamic Acid Decarboxylase (GAD) • GABA

  29. GABA Synapse

  30. GABAReceptors • GABAA receptors • GABAB receptors • GABAC receptors Iontotropic Metabotropic GABAA Receptor

  31. GABAA receptor properties

  32. GABA and Anxiety • Benzodiazepines (BDZ) and barbiturates cause sedation and reduced anxiety by binding to modulatory sites on the GABA receptor complex • BDZ binding sites are widely distributed in the brain. • They are in high concentration in the amygdala and frontal lobe. • Natural differences in anxiety levels are correlated with the number of BDZ binding sites. • PET scans of patients with panic disorder show less benzodiazepine binding in the CNS, particularly in the frontal lobe.

  33. The Science of Drug Action Pharmacology: study of the actions of drugs and their effects on living organisms. Neuropharmacology: study of drug-induced changes in nervous system cell functioning. Psychopharmacology: emphasizes drug-induced changes in mood, thinking, and behavior. Neuropsychopharmacology: identifies chemical substances that act on the nervous system to alter behavior. .

  34. The Science of Drug Action Drug action: molecular changes produced by a drug when it binds to a target site or receptor. Drug effects:The molecular changes that alter physiological or psychological functions. Therapeutic effects: the drug–receptor interaction produces desired physical or behavioral changes. Side effects: all other non-therapeutic effects. Specific drug effects: are based on physical and biochemical interactions of a drug with a target site in living tissue. Nonspecific drug effects: are based on certain unique characteristics of the individual, (e.g., mood, expectations, perceptions, attitudes, placebo effects).

  35. Therapeutic Index • Effective dose • dose of a drug that produces a meaningful effect in some percentage of test subjects • ED50 = effective dose for half the animals in a drug test • Lethal dose • dose of a drug that has a lethal effect in some percentage of test subjects • LD50 = lethal dose for half the animals in a drug test • Therapeutic index = LD50/ED50 • Always greater than one • Most drugs have an LD1 well above the ED95

  36. Pharmacokinetic Factors

  37. 1. Drug Route of Administration

  38. 2. Absorption and Distribution • Lipid Solubility • Ionization • pH • Stomach Content • Gender • Other • BBB • Placenta

  39. 3. Drug Binding • Drugs bind to proteins in blood, or temporarily stored in bones or fat cells (inactivating drug) • Reduces the concentration of drug at site of action • Competition of binding can alter the concentration of free active drug potentially leading to overdose • Drug is not altered by liver enzymes • Can terminate action of drugs

  40. 4. Inactivation (Biotransformation)

  41. 5. Excretion • Organs: • Intestines • Kidneys • Lungs • Sweat glands • Products: • Feces • Urine • Water Vapor • Sweat • Saliva

  42. Mechanism of Drug Action • Effects on specific neurotransmitter systems: • Drugs may alter the availability of a neurotransmitter by changing the rate of: • Synthesis • Metabolism • Release • Reuptake • Drugs may activate or prevent the activation of a receptor

  43. Drugs can acts as Agonists Agonist binds and has same effect as endogenous neurotransmitter, channel opens Normal receptor at rest, channel is closed Neurotransmitter binds receptor and opens channel

  44. Drugs can act as Antagonists Typical antagonist binds in place of endogenous neurotransmitter, prevents neurotransmitter action Non-competitive binding antagonist doesn’t interfere with neurotransmitter binding but still prevents neurotransmitter action

  45. Presynaptic Drug Actions 8. Blockade of NT degradation MAO inhibitors Prozac Chemical Weapons

  46. Postsynaptic Drug Actions

More Related