Chapter 24 Chemical Communications Neurotransmitters & Hormones

Transcription

1 Chapter 24 Chemical Communications Neurotransmitters & Hormones 1

2 Chemical Communication Terms and definitions: Neuron: A nerve cell. Neurotransmitter: A chemical messenger between a neuron and another target cell; a neuron, muscle cell or cell of a gland. Hormone: A chemical messenger released by an endocrine gland into the bloodstream and transported therein to reach its target cell. 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). 2

3 Chemical Communications There are three principal types of molecules for communications. Receptors: Protein molecules that bind ligands and effect some type of change. Chemical messengers: also called ligands, interact with receptors. They fit into receptor sites in a manner reminiscent of the lock-and-key model of enzyme action. Secondary messengers: In many cases, carry a message from a receptor to the inside of a cell and amplify the message. 3

4 Chemical Communications A large percentage of the drugs we encounter in medical practice try to influence chemical communications. A drug may affect either a messenger, a receptor, a secondary messenger, or an enzyme that is activated or inactivated as part of a metabolic pathway. An antagonist drug blocks a receptor and prevents its stimulation. An agonist drug competes with a natural messenger for a receptor site. Once there it stimulates the receptor. Other drugs increase the concentration of a messenger by inhibiting its removal from its receptors. Still other drugs inhibit or activate specific enzymes inside cells. 4

5 Chemical Messengers There are five classes of chemical messengers: Cholinergic messengers Amino acid messengers Adrenergic messengers Peptidergic messengers Steroid messengers Chemical 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 5

6 Acetylcholine Acetylcholine (ACh) is the main cholinergic messenger. 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. 6

7 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 0.1 µm, 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. 7

8 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 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. 8

9 Acetylcholine Figure 24-3 Acetylcholine in action. 9

10 Acetylcholine Removal of ACh ACh is removed from a receptor site by hydrolysis catalyzed by the enzyme acetylcholinesterase. This rapid removal allows nerves to transmit more than 100 signals per second. 10

11 Control of neurotransmission Acetylcholinesterase is inhibited irreversibly by the phosphonates in nerve gases and some pesticides. It is inhibited by succinyl chloride (Chemical Connections 23A) and decamethonium bromide. 11

12 Acetylcholine Control of transmission (cont d) Another control is to modulate the action of the ACh receptor. Because ACh enables ion channels to open and propagate signals, the channels themselves are called ligand-gated ion channels. The binding 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 large doses is an antagonist and blocks the action of the receptor. 12

13 Amino Acids Messengers Amino acid messengers Some amino acids are excitatory neurotransmitters; examples are Glu, Asp, and Cys. Others are inhibitory neurotransmitters; they reduce neurotransmission. Examples are Gly and these three, none of which is found in proteins. 13

14 Amino Acid Messengers Each amino acid has its own receptors Glu has at least five subclasses of receptors. The best known receptor 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. The gate of this channel is closed by Mg 2+ ion. Glu is removed by reuptake, which is facilitated by transporter molecules. 14

15 Adrenergic Messengers Monoamine messengers These monoamines transmit signals by a mechanism whose beginning is similar to the action of acetylcholine, that is, they are absorbed on a receptor. 15

16 End 10/5/16 class 16