1. 23 23-1 © 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

2. 23 23-2 © 2003 Thomson Learning, Inc. All rights reserved Chapter 23 Chemical Communication: Chemical Communication: Neurotransmitters and Hormones Neurotransmitters and Hormones

3. 23 23-3 © 2003 Thomson Learning, Inc. All rights reserved Introduction There are three principal types of molecules used for communications Receptors:Receptors: proteins embedded in the surface membranes of cells Chemical messengers:Chemical messengers: chemicals that interact with receptors; also called ligands Secondary messengers:Secondary messengers: chemicals that carry a message from a receptor to the inside of a cell and amplify the message

4. 23 23-4 © 2003 Thomson Learning, Inc. All rights reserved Introduction Other terms and definitions neuron:neuron: a nerve cell neurotransmitterneurotransmitter: a compound involved in communication between neurons or between a neuron and a target tissue; it acts across a synapse hormone:hormone: a compound that is synthesized in one location, travels large distances, usually in the blood, and then acts at a remote location (see Table 23.2) the distinction between a neurotransmitter and a hormone is physiological, not chemical; it depends on whether the molecule acts over a short distance (across a synapse) or over a long distance (from the secretory organ, through the blood, to its site of action)

5. 23 23-5 © 2003 Thomson Learning, Inc. All rights reserved Introduction A large percent of drugs used in human medicine influence chemical communication (see Table 23.1) antagonist:antagonist: a molecule that blocks a natural receptor and prevents its stimulation agonist: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

6. 23 23-6 © 2003 Thomson Learning, Inc. All rights reserved Introduction Neuron and synapse

7. 23 23-7 © 2003 Thomson Learning, Inc. All rights reserved Chemical Messengers There are five classes of chemical messengers cholinergic messengers amino acid messengers adrenergic messengers peptidergic messengers steroid messengers Messengers are also classified by how they work; they may activate enzymes affect the synthesis of enzymes affect the permeability of membranes act directly or through a secondary messenger

8. 23 23-8 © 2003 Thomson Learning, Inc. All rights reserved Acetylcholine The main cholinergic messenger is acetylcholine Cholinergic receptors there are two kinds of receptors for acetylcholine we look at the one that exists in motor end plates of skeletal muscles or in sympathetic ganglia

9. 23 23-9 © 2003 Thomson Learning, Inc. All rights reserved 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, Ca 2+ when Ca 2+ concentration becomes more that about 10 -4 M, 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

10. 23 23-10 © 2003 Thomson Learning, Inc. All rights reserved Acetylcholine Action of the acetylcholine (cont’d) the presence of ACh on the postsynaptic receptor triggers a conformation 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 it K + ions have higher concentration inside the neuron and leave it this change of Na + and K + ion concentrations is translated into a nerve signal after a few milliseconds, the ion channel closes

11. 23 23-11 © 2003 Thomson Learning, Inc. All rights reserved Acetylcholine

12. 23 23-12 © 2003 Thomson Learning, Inc. All rights reserved Acetylcholine Removal of ACh ACh is removed from the receptor site by hydrolysis catalyzed by the enzyme acetylcholinesterase this rapid removal allows nerves to transmit more than 100 signals per second

13. 23 23-13 © 2003 Thomson Learning, Inc. All rights reserved Acetylcholine Control of neurotransmission acetylcholinesterase is inhibited irreversibly by the phosphonates in nerve gases and some pesticides (ChemCom 23B) it is also inhibited by these two compounds

14. 23 23-14 © 2003 Thomson Learning, Inc. All rights reserved Acetyl Choline Control of transmission (cont’d) another control is to modulate the action of the ACh receptor ligand-gated ion channelsbecause ACh enables ion channels to open and propagate signals, the channels themselves are called ligand-gated ion channels the attachment of the ligand to the receptor is critical to signaling nicotine in low doses is a stimulant; it is an agonist because it prolongs the receptor’s biochemical response nicotine in high doses is an antagonist and blocks the action of the receptor

15. 23 23-15 © 2003 Thomson Learning, Inc. All rights reserved Amino Acids Amino acid messengers excitatory neurotransmitterssome amino acids are excitatory neurotransmitters; examples are Glu, Asp, and Cys inhibitory neurotransmittersothers are inhibitory neurotransmitters; examples are Gly and these three

16. 23 23-16 © 2003 Thomson Learning, Inc. All rights reserved Amino Acid Messengers Receptors Glu has at least five subclasses of receptors the best known among these is the N-methyl-D- aspartate (NMDA) receptor this receptor is a ligand-gated ion channel when Glu binds to the receptor, the ion channel opens, Na + and Ca 2+ ions flow in, and K + ions flow out NMDA is an agonist and also stimulates the receptor

17. 23 23-17 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers Monoamine messengers

18. 23 23-18 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers When norepinephrine is absorbed onto the receptor site the active G-protein hydrolyzes GTP the energy of hydrolysis activates adenylate cyclase

19. 23 23-19 © 2003 Thomson Learning, Inc. All rights reserved Cyclic AMP (cAMP) cAMP is synthesized in cells from ATP

20. 23 23-20 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers cyclic AMP activates protein kinase by dissociating the regulatory (R) unit from the catalytic (C) unit

21. 23 23-21 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers the catalytic unit phosphorylates the ion-translocating protein that blocks the channel ion flow the phosphorylated ion-translocating protein changes its shape and position and opens the ion gate

22. 23 23-22 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers Removal of the signal when the neurotransmitter or hormone dissociates from the receptor, adenylate cyclase stops the synthesis of cAMP the cAMP already produced is destroyed by the enzyme phosphodiesterase, which catalyzes the hydrolysis of one of the phosphodiester bonds to give AMP

23. 23 23-23 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers Control of neurotransmission the G-protein-adenylate cyclase cascade in transduction signaling is not limited to monoamine messengers among the other neurotransmitters and peptide hormones using this signaling pathway are glucagon, vasopressin, luteinizing hormone, enkephalins, and P- protein a number of enzymes can be phosphorylated by protein kinases and the phosphorylation controls whether these enzymes are active or inactive

24. 23 23-24 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers Removal of neurotransmitter the body inactivates monoamines by oxidation to an aldehyde, catalyzed by monoamine oxidases (MAOs)

25. 23 23-25 © 2003 Thomson Learning, Inc. All rights reserved Adrenergic Messengers Histamine H 1 receptors are found in the respiratory tract where they affect the vascular, muscular, and secretory changes associated with hay fever and asthma; antihistamines that block H 1 receptors relieve these symptoms H 2 receptors are found mainly in the stomach and affect the secretion of HCl; cimetidine and ranitidine block H 2 receptors and thus reduce acid secretion

26. 23 23-26 © 2003 Thomson Learning, Inc. All rights reserved Peptidergic Messengers The first brain peptides isolated were the enkephalins these pentapeptides are present in certain nerve cell terminals they bind to specific pain receptors and seem to control pain perception Neuropeptide Y, a potent orexic, affects the hypothalamus Substance P, an 11-amino acid peptide is involved in the transmission of pain signals

27. 23 23-27 © 2003 Thomson Learning, Inc. All rights reserved Peptidergic Messengers All peptidergic messengers, hormones, and neurotransmitters act through secondary messengers glucagon, luteinizing hormone, antidiuretic hormone, angiotensin, enkephalin, and substance P use the G- protein-adenylate cyclase cascade others such as vasopressin use membrane-derived phosphatidylinositol (PI) derivatives

28. 23 23-28 © 2003 Thomson Learning, Inc. All rights reserved Steroid Messengers A large number of hormones are steroids these hormones are hydrophobic and, therefore, cross plasma membranes by diffusion steroid hormones interact inside cells with protein receptors most of these receptors are located in the nucleus, but small numbers also exist in the cytoplasm once inside the nucleus, the steroid-receptor complex can either bind directly to DNA or combine with a transcription factor

29. 23 23-29 © 2003 Thomson Learning, Inc. All rights reserved End Chapter 23 Chemical Communication