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Chemical Messengers Neurotransmitters Hormones Supplemental © 2013 Pearson Education, Inc. Chapter 18, Section 6 4/13/2013 Chemical Messengers: for coordination of biological processes within an organism Terms and Definitions: neuron: a nerve cell. neurotransmitter: a chemical messenger between a neuron and another target cell; neuron, muscle cell or cell of a gland. - the molecule acts over a short distance (across a synapse, ~ 0.1 µm) Eg, Acetylcholine hormone: a chemical messenger released by an endocrine gland (secretary organ) into the bloodstream and transported there to reach its target cell (its site of action). over a long distance (~ 20cm). Eg, Insulin © 2013 Pearson Education, Inc. Chapter 18, Section 6 Chemical Messengers Five Classes: : Cholinergic Messengers: Acetylcholine, and likes Amino acid Messengers: Glutamate, GABA, etc. Adrenergic Messengers: Monoamines Peptidergic Messengers: Insulin, Glucagon, etc. Steroid Messengers: Androgen, Estrogen, etc. Messengers are also classified by how they work; activate enzymes. affect the synthesis of enzymes. affect the permeability of membranes. act directly or through a secondary messenger. © 2013 Pearson Education, Inc. Chapter 18, Section 6 Chemical Communication Many drugs used in medicine influence chemical communication Antagonist: a molecule that blocks a natural receptor and prevents its stimulation. Agonist: a molecule that competes with a natural messenger for a receptor site; it binds to the receptor site and elicits the same response as the natural messenger. A drug may decrease or increase the effective concentration of messenger. © 2013 Pearson Education, Inc. Chapter 18, Section 6 A neurotransmitter © 2013 Pearson Education, Inc. Chapter 18, Section 6 5 Acetylcholine (ACh): the main cholinergic messenger the first neurotransmitter found (1914) by Henry Dale & Otto Loewi (NP, 1936) communicate between the nervous system and the muscle. When stimulated, it releases into the synapse where it binds to muscle cell receptors causing the muscles to contract. O CH3 CH3 -C-O-CH2 -CH2 + -N-CH3 CH3 Acetylch oline (A Ch ) © 2013 Pearson Education, Inc. Amine (Quaternary) as well as Esther Chapter 18, Section 6 6 Acetylcholine Storage and release of acetylcholine (ACh). The nerve cells that bring messages contain ACh stored in vesicles. The receptors on muscle neurons are called nicotinic receptors because nicotine inhibits them. The message is initiated by calcium ions, Ca2+. When Ca2+ concentration becomes more than about 0.1 mM, the vesicles that contain ACh fuse with the presynaptic membrane of nerve cells and empty ACh into the synapse. ACh travels across the synapse and is absorbed on specific receptor sites. © 2013 Pearson Education, Inc. Chapter 18, Section 6 Acetylcholine Action of the acetylcholine (cont’d) The presence of ACh on the postsynaptic receptor triggers a conformational change in the receptor protein. This change opens an ion channel and allows ions to cross membranes freely. Na+ ions have higher concentration outside the neuron and pass into the cell. K+ ions have higher concentration inside the neuron and leave the cell This change of Na+ and K+ ion concentrations is translated into a nerve signal. After a few milliseconds, the ion channel closes. © 2013 Pearson Education, Inc. Chapter 18, Section 6 Acetylcholine in Action © 2013 Pearson Education, Inc. Chapter 18, Section 6 Acetylcholine Removal of ACh ACh is removed from the receptor site by hydrolysis catalyzed by the enzyme acetylcholinesterase. Acetylch olin O CH3 es teras e CH3 -C-O-CH2 -CH2 + -N-CH3 + H2 O CH3 A cetylcholine (ACh) O CH3 + CH3 -C-O + HO-CH2 -CH2 -N-CH3 CH3 Choline Acetate This rapid removal allows nerves to transmit more than 100 signals per second. © 2013 Pearson Education, Inc. Chapter 18, Section 6 Acetylcholine Acetylcholine is linked to Alzheimer’s disease In Alzheimer’s disease, ACh levels may decrease by 90%. Aricept, an Alzheimer’s medication, slows the breakdown of ACh in order to elevate the acetylcholine levels in the brain. © 2013 Pearson Education, Inc. Chapter 18, Section 6 12 Catecholamines © 2013 Pearson Education, Inc. Include dopamine, norepinephrine, and epinephrine All of these are closely related in structure and all are synthesized from the amino acid tyrosine. Chapter 18, Section 6 13 Dopamine produced in the nerve cells of the midbrain and acts as a natural stimulant to give us energy and feelings of enjoyment. Control muscle movement, improve, cognition, memory, & learning Cocaine and amphetamine block the reuptake of dopamine resulting in a longer lifetime in synapse. © 2013 Pearson Education, Inc. Chapter 18, Section 6 14 Norepinephrine and Epinephrine Norepinephrine (noradrenaline) and epinephrine (adrenaline) are hormonal neurotransmitters that play a role in sleep, attention and focus, and alertness. Epinephrine is synthesized from Norepinephrine. Both are normally produced in the adrenal glands. Both are highly produced during the fight-or-flight response, increasing blood pressure, heartv rate, constrict blood vessel, dilate airways, stimulating breakdown of glycogen. Administered during cardiac arrest.broncodialator. Low level leads to Attention Deficit Disorder(ADD) © 2013 Pearson Education, Inc. Chapter 18, Section 6 15 Serotonin (5-Hydroxytryptamine) Serotonin helps us relax, sleep deeply and peacefully, think rationally, and it provides us a feeling of well-being and calmness. Serotonin is synthesized from the amino acid tryptophan. Psychedelic drugs stimulate the action of serotonin at its receptors. Low serotonin levels may be associated with depression, anxiety disorders, etc. Prozac and Paxil (antidepressant drugs) are selective serotonin reuptake inhibitors (SSRIs). © 2013 Pearson Education, Inc. Chapter 18, Section 6 16 Prozac and Paxil © 2013 Pearson Education, Inc. Chapter 18, Section 6 17 Histamine synthesized in the nerve cells in the hypothalamus from the amino acid, histidine. is produced by the immune system in response to pathogens and invaders, or injury. When it combines with histamine receptors, it produces allergic reactions – inflammation, watery eyes, itchy skin,.etc. © 2013 Pearson Education, Inc. Chapter 18, Section 6 18 Amino Acid Neurotransmitters Glutamate the most abundant neurotransmitters in the nervous system. stimulates the synthesis of nitrogen monoxide (NO). Both Glutamate & NO involved in learning and memory Too much glutamate in the spinal cord causes degeneration of nerve cells (Lou Gehrig’s disease of Muscular atrophy). Too rapid uptake of glutamate may results in schizophrenia: © 2013 Pearson Education, Inc. Chapter 18, Section 6 19 Gamma(g)-Aminobutyric Acid (GABA) the most common inhibitory neurotransmitter in the brain. produces a calming effect by inhibiting the ability of nerve cells to send electrical signals to nearby nerve cells. Alcohol, & sedatives increases the inhibitory effects. Caffeine decreases the GABA levels in the synapses causing opposite effects. © 2013 Pearson Education, Inc. Chapter 18, Section 6 20 © 2013 Pearson Education, Inc. Chapter 18, Section 6