Small Molecule Neurotransmitters PDF

Small molecule NTM ACETYLCHOLINE (ACH) Organic chemical found in various parts of the body esp neuromuscular junctions and ANS Parts of the body that uses acetylcholine are called CHOLINERGICS Those that interfere with ACH are called anticholinergics Acet...

Small molecule NTM ACETYLCHOLINE (ACH) Organic chemical found in various parts of the body esp neuromuscular junctions and ANS Parts of the body that uses acetylcholine are called CHOLINERGICS Those that interfere with ACH are called anticholinergics Acetylcholine Secreted by: (1) the terminals of the large pyramidal cells from the motor cortex, (2) basal nuclei (3) the motor neurons that innervate the skeletal muscles (4) the preganglionic neurons of the autonomic nervous system (5) the postganglionic neurons of the parasympathetic nervous system (6) some of the postganglionic neurons of the sympathetic nervous system (not common) Acetylcholine mostly excitatory effect-muscles incl GI some inhibitory effects i.e., such as inhibition of the heart by the Vagus cranial nerve. Known for its role in memory and learning Alzheimer’s Disease associated with breakdown of acetylcholine neurons ACETYLCHOLINE (ACH) Commonly binds with nicotinic and muscarinic receptors These receptors care cumulatively called cholinergic receptors ACETYLCHOLINE (ACH) Nicotinic receptors commonly found on muscle cells, CNS, ANS. Integral for movement; Ionotropic receptor Muscarinic receptors commonly found in both CNS, PNS of the heart, lungs, upper GI tract and sweat glands Metabotropic receptor use a G-protein. When ACh binds to the receptor, this special protein changes shape, which then allows it to phosphorylate various second messengers. Acetylcholine synthesis Post synapse: Acetylcholine (broken down by acetylcholinesterase) Choline and Acetate -CHOLINE transported back to the presynaptic neuron for resynthesis -ACETATE is excreted or - reused as Acetyl CoA (combination of acetate and coenzyme A molecules: important for protein, carb, lipid metabolism) Acetylcholine synthesis Post synapse: Choline in the Presynaptic neuron PLUS Acetyl CoA via acetyl transferase New ACH synthesized Norepinephrine (NE) secreted by: 1) in the brain stem and hypothalamus. 2) pons (control of overall activity and mood of the mind, i.e., wakefulness) 3) most postganglionic neurons of the sympathetic nervous system (some excitatory, some inhibitory) activates excitatory receptors, but in a few areas, it activates inhibitory receptors Norepinephrine (NE) Also called noradrenaline (NA) Binds with noradrenergic receptors Commonly binds with alpha 1,2; beta 1,2,3 receptors STRESS decreases source of adrenalin, EXERCISE increases it Associated with putting our system on “high alert” Main NTM for SNS responsible for tonic and reflexive changes in cardiovascular tone. Important role in attention and concentration Synthesis of NE and dopamine (dopamine a precursor of NE) Phenylalanine (essential amino acid) (via enzyme phenylalanine hydroxylase) Tyrosine (non essential amino acid) Hydroxylation (via enzyme tyrosine hydroxylase) L dopa (via enzyme DOPA decarboxylase, Decarboxylation conversion in the cytoplasm) Dopamine Hydroxylation (via enzyme dopamine monooxygenase, conversion occurs in NTM vesicles) Norpinephrine Epinephrine (EPI) Also known as adrenalin / adrenaline Produced by adrenal glands and some neurons. Binds with adrenergic receptors Responsible for flight or fight response (ANS) Epinephrine Adrenaline Highly responsive to metabolic or global challenges to homeostasis, such as glucoprivation, and manifestations of emotional distress. EPI Pen: Use to treat cardiac arrest, anaphylaxis, hypoglycemia, bronchospasm Epinephrine synthesis from NE (via enzyme Methylation phenylethanolamine N Methyltransferase Epinephrine Dopamine secreted by neurons that originate in the substantia nigra; the termination of these neurons is mainly in the striatal region of the basal nuclei The effect is usually inhibition. Blocks the tendency of neuron to fire. Binds with dopaminergic receptors Decreased (Parkinson’s); Increased (related to schizophrenia) Dopamine Outside of the CNS: blood vessels vasodilation by inhibiting norepinephrine release Kidneys: Increases sodium excretion and urine output; Pancreas: decreased insulin production; Digestive system: decreased gastrointestinal motility and protection of intestinal mucosa; Immune system: decreased activity of the lymphocytes  Norepinephrine degradation: Reuptake into adrenergic nerve endings via active transport, removing 50-80% of NE Diffusion away from the nerve endings into surrounding body fluids then into the blood, removing most of the remaining NE Destruction of small amounts by tissue enzymes (monoamine oxidase {MAO} found in nerve endings and catechol-O-methyl transferase, present diffusely in tissues)  Norepinephrine degradation: NE secreted directly into the tissue: only active for a few seconds (rapid reuptake and diffusion) NE and EPI secreted into the blood by adrenal medullae remain active until diffused into some tissue, destroyed by catechol o methyl transferase (mainly happens in the liver) When secreted in the blood, NE and EPI remain active for 10-30 seconds and goes into extinction over 1 to several minutes  Receptors on Effector organs: NTM binds with receptors before they can stimulate an effector organ Found outside of the cell membrane Binding of NT with receptor causes a change in the structure of the protein molecule causing an excitation nor inhibition by: Change in membrane permeability to one or more ions Activating or inactivating an enzyme attached to the other end of the receptor protein, protruding to the interior of the cell GLYCINE secreted mainly at synapses in the spinal cord, brain stem and retina In some areas of CNS, released together with GABA participates in the processing of motor and sensory information that permits movement, vision, and audition. believed to always act as an inhibitory transmitter. binds with Glycinergic receptors Glycine synthesis Non essential amino acid (biosynthesized from amino acid serine hydroxymethyltransferase) Catalyzed by glycine synthase Can be readily converted GABA (gamma-aminobutyric acid) secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia, and many areas of the cortex. It is believed always to cause inhibition. PRIMARY INHIBITORY NTM OF CNS GABA Directly responsible for regulation of muscle tone Binds to GABAergic receptors Acts as a “brake” to the excitatory neurotransmitters causing to anxiety If decreased, people suffer from anxiety GABA Very important. Believed that brain works primarily through inhibition and not excitation, Keep the neural signal organized and segmented Important in physiological and behavioral processes Valium (diazepam), commonly prescribed medicine for anxiety, increases GABA activity GABA GABA receptors: ligand-activated chloride channels When activated, allows flow of Cl- ions When Cl- is flowing out of the cell, GABA is depolarizing When Cl- is flowing into the cell, GABA is hyperpolarizing and performing its inhibitory function GABA synthesis Glutamate (via enzyme glutamate decarboxylase) GABA Glutamate secreted by the presynaptic terminals in many of the sensory pathways entering the central nervous system many areas of the cerebral cortex. It probably always causes excitation. Toxic to the brain if in excess (Lou Gehrig’s disease (ALS) related to excessive glutamate production-resulting to too much cell activity leading to cell death) Glutamate GABA’s counterpart PRIMARY EXCITATORY NTM OF THE CNS Implicated as particularly important in LEARNING AND MEMORY Binds to glutaminergic receptors – can result to alterations in neural synapses, forming new connections, therefore leading to neural basis for new memories Glutamate synthesis Glutamate converted to glutamine (via glutamine synthetase) glutamine taken into the presynaptic terminal for resynthesis (packaged back into the synaptic vesicles) then metabolized back into glutamate via glutaminase Serotonin secreted by nuclei that originate in the median raphe of the brain stem many brain and spinal cord areas, especially to the dorsal horns of the spinal cord and to the hypothalamus. Serotonin acts as an inhibitor of pain pathways in the cord. RELATED TO EMOTIONS AND MOODS Decreased serotonin: depression, anger, obsessive compulsive disorder, suicide, increased appetite for carbohydrates, sleeping disorder Serotonin 90% of total serotonin found in the GI tract (regulation of intestinal movements) Serotonin needed for healthy sleep and stable moods Binds to serotonergic receptors Warm milk before bed time increases serotonin. From Tryptophan (essential amino acid, means your body needs it but does not produce it, therefore has to be included in diet). Found in milk, cheeses, egg whites, nuts, seeds, tofu, chicken, red meat, turkey, fish, oats, beans Serotonin synthesis Tryptophan (via enzyme tryptophan hydroxylase) Hydroxytryptophan (via enzme L-amino acid decarboxylase) Serotonin Nitric oxide (gaseous NTM) secreted by nerve terminals in areas of the brain responsible for long-term behavior and for memory.. Synthesis different than other NTM: It is not preformed and stored in vesicles in the presynaptic terminal; Instead synthesized almost instantly as needed and diffused over a period of seconds After diffusion in the post synaptic terminal, it does not alter membrane potential, it changes INTRACELLULAR METABOLISM (that modifies neuron excitability from a few seconds to longer than minutes)