Class notes - week of 10/26
Class notes - week of 10/26 CHEM 2410
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This 11 page Class Notes was uploaded by Emma Notetaker on Friday October 30, 2015. The Class Notes belongs to CHEM 2410 at Tulane University taught by Carol Zhang in Summer 2015. Since its upload, it has received 18 views.
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Date Created: 10/30/15
Neurotransmitters 102315 832 PM 0 criteria 0 1 synthesized and stored in presynaptic terminal 0 immunohistochemistry use of antibody to identify where neurotransmitters are determines whether nt in vesicle main technique for nt location and whether or not chemical is neurotransmitter generate antibody for chemical by injecting animal with chemical to make antibodies will stick to antigen sites when applied to brain slice 0 2 released from terminals with stimulation 0 chemical assay take up ECF assay for chemical 0 determined by chemical response 0 3 specific receptors on postsynaptic cells 0 neuropharmacology using agonists or antagonist to stimulate or block receptors 0 autoradiography using radiotagged or fluorescenttagged neurotransmitters to see where it sticks to find receptors 0 discovery of neurotransmitters 0 transmission of nerve signal electrical or chemical experiment by Otto Loewi 1921 confirms neuron doctorine o 2 hearts in separate chambers connected by tube so ONLY fluid could flow no electrical connection 0 stimulation of vagus nerve of 1 0 transfer of medium to 2nd 0 results 1St heart decreased rate and contraction vagus nerve stimulated 2nd heart ALSO decreased after first one SO chemical connection between chambers through fluidnot electrical chemical transmission of signal transmitter ACh vagusstoff 0 types 3 classes 0 1 small molecule nt 3 subgroups o 1 amino acids glutamate excitatory GABAglycine inhibitory o 2 ACh o 3 biogenic amines catecholamines a dopamine n norepinephrine n epinephrine serotonin histamine 2 neuropeptides all use Gprotein coupled receptors metabotropic o peptide packaged into vesicles and released by neurons 0 release from neurons near synapses acts as nt neurohumeral junctions synapses on blood vessels n acts as neurohormone a mostly contained in hypothalamus controls ANS and endocrine 0 types hypothalamic peptides opiates gut peptides 3 unconventional nt 0 gases I NO I CO 0 lipids endocannabinoids made in plasma membrane lipase converts lipid into endocannabinoid released during production 0 growth factorscytokines neurotransmitters are PROTEINS 3 classes 0 1 cytosolic synthesized by free ribosomes transported by slow axoplasmic fibrillar cytoskeleton and enzymes metabolic triggers where small molecule neurotransmitters come from u made from enzymes and precursors o 2 nuclear proteins 0 3 membrane associated proteins made by ribosomes stuck to RER types a 1 integral and peripheral proteins a 2 ER proteins a 3 vesicle associated proteins lysosomes secretory products enzymes synthesis transport packaging 1 small molecule 0 00000 synthesis of metabolic enzymes work on precursors cytosolic proteins taken transported into vesicles slow axoplasmic transport synthesis of transmitter uptake into synaptic vesicles release 0 2 neuropeptides O 0000 0 synthesis of precursor proteins packaging into vesicles into Golgi apparatus membrane proteins fast anterograde transport along microtubules gets to axon terminal peptides ready in vesicles ready for release not recycled or charged within vesicles cleavage of precursors by enzymes into final neurotransmitter product release neurotransmitter fate at synapse 0 can be uptake by presynaptic terminal or postsynaptic O uptake from presynaptic goes into repackaging of small molecule neurotransmitter to recycle 0 diffusion terminates response 0 exocytosis triggers endocytosis o reuptake of neurotransmitter or breakdown of neurotransmitter retransported by vesicular transporters on membrane put nt back into vesicles to recharge vesicles 0 neuropeptides usually packaged in densecore vesicles larger and more dense core than vesicles from small molecule transmitters 0 these vesicles are black under TEM o vesiclaes are off active site back a little further 0 released outside synapse farther back 0 responsible for volume transmission not at synapse but released into extracellular space add to volume and increase concentration in peptide in cytoplasm can be activating receptors anywhere in vicinity corelease of both types of transmitters peptides and small molecule 0 colocalization of nt 0 small molecule nt and neuropeptides often located in same terminals 0 corelease different locations of vesicles 0 synaptic vesicles small clocked at membrane 0 large densecore vesicles off membrane out of active zone takes priming to get them to move to membrane 0 different exocytosis conditions 0 low frequency firing 9 low calcium concentration 9 small molecule nt release readily releasable pool 0 high frequency firing 9 high ca concentration 9 small molecule AND neuropeptide release takes a lot of calcium to reach the area of neuropeptides because farther back often neuropeptides release modulates small molecule release slow response modulates fast response amino acids 0 packaged at axon terminal into vesicles 0 recycled at terminal into synaptic vesicles glutamate excitatory usually extrinsic projection project outside their area all over the brain principal neurons synthesis in terminal precursor glutamine catalyzed by glutaminase recognized by vesicular transporter release postsynaptic receptors n ionotropic AMPA kainite NMDA n metabotropic mGluRl mGluR8 termination of actions diffusion and uptake taken up by astrocytes EA39IT a broken down into precursor glutamine through glutamine synthetase n glutamine leaves astrocyte goes into axon terminal via glutamate transporters a recycled made into glutamate again GABA inhibitory 0 usually inhibitory interneurons intrinsic projections within a structure link up principal neurons synthesis in terminal glutamate is precursor catalyzed by glutamic acid decarboxylase GAD pyridoxal phosphate packaging in vesicles by vesicular transporter release receptors n ionotropic GABAA Cl channel a metabotropic GABAB K and Ca channels indirectly reuptake taken up into astrocytes and neurons GABA transporters take them back to recycle recycling breakdown ACh 0 synthesis in terminal 0 precursors acetyl CoA choline aa via choline acetyltransferase 0 release receptors 0 nicotinic ionotropic o muscarinic metabotropic termination breakdown o acetylcholinesterase acetate choline o uptake of choline choline transporter resynthesis of ACh transmitter recycling cholinergic systems 0 central ACh system diffuse system project axons out 3 sources a 1 PMT pontomesencephalotegmental complex basal forebrain projections n 2 basal nucleus of meynart cortical projections 0 higher forebrain n 3 medial septum corticalhippocampal projections ACh fibers lost in Alzheimer s 0 memory involvement attention 0 Ach in ANS o sympathetic ACh in preganglionic neurons 0 parasympathetic ACh in preganglionic and postganglionic catecholamines dopamine norepinephrine noradrenaline epinephrine adrenaline 0 synthesis 0 precursor tyrosine aa tyrosine hydroxylase 9 DOPA DOPA decarboxylase 9 dopamine dopamine B hydroxylase 9 norepinephrine PNMT 9 epinephrine OOOO mood stress fluidenergy homeostasis reward autonomic fx 0 receptors 0 dopamine D1D4 o norepinephrine metabotropic a B o epinephrine metabotropic a B o 1 dopamine o diffuse modulatory systems 0 3 sources 1 ventral tegmental area a cortex frontal lobe projections n schizophrenia a reward 2 substantia nigra n striatum projections n Parkinson s a motor 3 basal hypothalamus n neuroendocrine n regulates anterior pituitary n prolactin secretion central neuroendocrine systems 0 pons o locus coeruleus o dorsal noradrenergic bundle corticalcerebellar projections spinal projections medulla brainstem NE system 0 solitary tract nucleus 0 ventrolateral medulla o ventral noradrenergic bundle subcortical projections diffuse projections involved in arousal and mood NE in ANS sympathetic o postganglionic neurons norepinephrine B receptors serotonin 5HT 0 synthesis 0 precursos tryptophan aa o tryptophan5hydroxylase 9 5hydroxytryptamine 5HT serotonin 0 receptors metabotropic 5HT1 through 5HT7 5HT4 thought to NOT be in the brain 5HT3 IONOTROPIC 0 systems 0 brainstem Raphe nuclei n9 diffuse projections a brain arousal mood sleepwake cycle a spinal cordpain hypothalamic neuropeptides 0 control of o pituitary gland neuroendocrine system 0 ANS descending neuronal projections homeostasis control center Neuropeptides magnocellular neuroendocrine cells 0 posterior pituitary 0 part of brain 0 neuropeptide secretion directly into general circulation oxytocin a contraction of smooth muscle in mammary glands to eject milk milk ejection reflex n parturition child birth 0 contraction of smooth muscle cells in uterus vasopressin antidiuretic hormone ADH blood volumeosmolality a response to dehydration and drop in blood pressure a fluid homeostasis n BP regulation neuropeptides parvocellular neuroendocrine cells 0 anterior pituitary control 0 1 releasing hormones secreted from hypothalamus mainly neuropeptides n GnRH n TRH n CRH corticotropin releasing hormone 0 stress response HPA axis leads to corticosteroid secretion from adrenal glands n GHRH a dopamine inhibitory and excitatory o 2 pituitary hormones secreted from anterior lobe of pituitary prolactin FSH and LH TSH ACTH growth hormone 102315 832 PM 102315 832 PM