Objectives1- Outline the criteria that need to be met before a molecule can be classified as “neurotransmitter”2- Identify the major neurotransmitter types3- Describe the major biochemical pathways for neurotransmitter synthesis and degradation4- Identify some clinical disorders that can arise as a result of disruption of neurotransmitter metabolism
NEUROTRANSMITTERSChemical transducers which are released byelectrical impulse into the synaptic cleft frompre-synaptic membrane from synapticvesicles.They then diffuse to the post-synapticmembrane and react and activate thereceptors present leading to initiation of newelectrical signals. 4
Types of responses on postsynaptic membrane• Excitatory postsynaptic potential (EPSPs)It is caused by depolarization.• Inhibitory Postsynaptic potential (IPSPs)It is caused by hyper-polarization.
NMDA =N methyl-D-aspartate receptors, when glutamate & glycine bind toreceptor ion channels open, Mg block channels
Gamma Aminobutyric acid (GABA)• It is one of the inhibitory neurotransmitter of CNS and is also found in retina.• It is formed by decarboxylation of glutamate.• The enzyme that catalyzes this reaction is glutamate decarboxylase(GAD)• There are three types of GABA receptors e.g. GABAA B & C.• GABA A & B receptors are widely distributed in CNS.• GABAC are found in retina only.• GABA B are metabotropic (G-protein) in function.
Glycine• It is simplest of all aminoacids, consisting of amino group and a carboxyl group attached to a carbon atom H+ H3 N+ C H+ Coo-
Glycine……..• Its an inhibitory neurotransmitter.• It binds to a receptor which makes the post synaptic membrane more permeable to Cl- Ion and cause hyperpolarization (inhibition).• The glycine receptor is primarily found in the ventral part of the spinal cord.• Strychnine is glycine antagonist.
Histamine• Three known types of histamine receptors in found e.g. H1, H2, H3.• H3 receptors are pre-synaptic. Its function in brain is not very certain. Its main function is that it is excitatory.
Nitric Oxide (NO)• NO is produced by arginine• Relax vascular and intestinal s. muscles• Role in mitochondrial energy production• Role in memory formation• Increased in Parkinsons and Alzheimers disease
Postsynaptic Site of PostsynapticNeurotransmitter Derived from Fate Functions effect synthesis receptor1.Acetyl choline Excitatory Acetyl co-A + Cholinergic •Nicotinic Broken by acetyl Cognitive functions(Ach) Choline nerve endings •Muscarinic cholinesterase e.g. memory Cholinergic Peripheral action e.g. pathways of cardiovascular brainstem system2. Catecholamines Excitatory in Tyrosine Adrenal Excites both •Catabolized to For details referi. Epinephrine some but produced in liver medulla and alpha α & inactive product ANS. e.g. fight or(adrenaline) inhibitory in from some CNS beta β through COMT & flight, on heart, other phenylalanine cells receptors MAO in liver BP, gastrointestinal •Reuptake into activity etc.ii.Norepinephrine Excitatory Tyrosine, found Begins inside α1 α2 adrenergic nerve Norepinehrine in pons. axoplasm of β1 β2 endings controls attention & Reticular adrenergic •Diffusion away arousal. formation, locus nerve ending is from nerve endings coerules, completed to body fluid thalamus, mid- inside the brain secretary vesiclesiii. Dopamine Excitatory Tyrosine CNS, D1 to D5 Same as above Decreased dopamine concentrated in receptor in parkinson’s basal ganglia disease. and dopamine Increased dopamine pathways e.g. concentration causes nigrostriatal, schizophrenia mesocorticolim bic and tubero- hypophyseal pathway
Postsynaptic Site of PostsynapticNeurotransmitter Derived from Fate Functions effect synthesis receptor 3. serotonin Excitatory Tryptophan CNS, Gut 5-HT1 to 5-HT Inactivated by MAO Mood control, sleep, (5HT) (chromaffin to form 5- pain feeling, 7 cells) Platelets 5-HT 2 A hydroxyindoleacetic temperature, BP, & & retina acid(5-HIAA) in hormonal activity receptor mediate pineal body it is platelet converted to aggregation & melatonin smooth muscle contraction4. Histamine Excitatory Histidine Hypothalamus Three types H1, Enzyme diamine Arousal, pain H2 ,H3 receptors oxidase threshold, blood found in (histaminase) cause pressure, blood flow peripheral tissues breakdown control, gut & the brain secretion, allergic reaction (involved in sensation of itch)5. Glutamate Excitatory By reductive Brain & spinal Ionotropic and It is cleared from the Long term 75% of amination of cord e.g. metabotropic brain ECF by Na + potentiation involved excitatory Kreb’s cycle hippocampus receptors. dependent uptake in memory and transmission intermediate Three types of system in neurons learning by causing in the brain α –ketoglutarate. ionotropic and neuroglia. Ca++ influx. receptors e.g. NMDA, AMPA and kainate receptors.
Postsynaptic Site of PostsynapticNeurotransmitter Derived from Fate Functions effect synthesis receptor Aspartate & Glycine form an excitatory /6. Aspartate Excitatory Acidic amines Spinal cord Spinal cord inhibitory pair in the ventral spinal cord GABA – A increases the Cl - GABA – A causes conductance, hyperpolarization Decarboxylation GABA – B is (inhibition) of glutamate by metabotropic Anxiolytic drugs like Metabolized by7. Gama amino Major glutamate works with G – benzodiazepine cause transamination tobutyric inhibitory decarboxylase CNS protein GABA increase in Cl- entry succinate in the citricacid(GABA) mediator (GAD) by transaminase into the cell & cause acid cycle. GABAergic catalyzes. soothing effects. neuron. GABA – C GABA – B cause found increase conductance exclusively in of K+ into the cell. the retina. Deactivated in the Is simple amino Glycine receptor Glycine is inhibitory synapse by simple acid having makes transmitted found in process of amino group and postsynaptic the ventral spinal8. Glycine Inhibitory Spinal cord reabsorbtion by active a carboxyl group membrane more cord. It is inhibitory transport back into attached to a permeable to Cl- transmitter to the presynaptic carbon atom ion. Renshaw cells. membrane