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ENDO-01.docx

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Physiology
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PSL201Y1
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Yue Li

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5 CHEMICAL MESSENGERS Mechanisms of Intercellular Communication DIRECT COMMUNICATION THROUGH GAP JUNCTIONS  Gap junctions link adjacent cells and arm formed by plasma membrane proteins, called connexins that form structures called connexons.  The movement of ions through gap junctions electrically couples the cells, such that electrical signals in one cell are directly transmitted to the neighboring cells.  The movement of small molecules through gap junctions metabolically couples the cells, such that one cell can provide necessary nutrients to other cells. INDIRECT COMMUNICATION THROUGH CHEMICAL MESSENGERS  Cells communicate via chemical messengers, which are all ligands, molecules that bind to proteins reversibly.  Communication through chemical messengers occurs when one cell releases a chemical into the interstitial fluid (secretion) and the target cell responds to the chemical messenger.  A target cell responds beause it has certain proteins called receptors, that specifically recognize and bind the messenger.  The binding of messengers to receptors produces a response in target cell through a variety of mechanisms referred to as signal transduction.  The strength of the target cell response increases as the number of bound receptors increases.  Number of bound receptors depends on both the [messengers] in the interstitial fluid and the [receptors] on the target cell. Chemical Messengers FUNCTIONAL CLASSIFICATION OF CHEMICAL MESSENGERS  Three main categories: paracrines, neurotransmitters, hormones.  Paracrines: chemicals that communicate with neighboring cells. Target cell must be close enough in order for the paracrine to reach by simple diffusion. Include growth factors, clotting factors, and cytokines. o Growth factors: proteins that stimulate proliferation and differentiation of cells. o Clotting factors: proteins that stimulate formation of a blod clot. o Cytokines: peptides released from immune cells that function in coordinating the body’s defense against infections. Most function as paracrines, but some travels like hormones. o Histamine: a chemical important in allergic reactions and inflammation and is secreted by mast cells scattered throughout the body. It increases blood flow to affected tissues (producing redness) and causes fluid to leak out of the blood vessels and into the tissue (producing swelling). o Autocrines: act on the same cell that secreted them. Secretory cell is also the target cell.  Neurotransmitters: chemicals released into the interstitial fluid from nervous system cells called neurons. Released from axon terminals, which are very close to the target cell. o Junction between the two cells is called a synapse (synaptic signaling). o Presynaptic neuron: the cell that releases the neurotransmitter. o Postsynaptic cell: the target cell (neuron, gland, or muscle cell). o It quickly diffuses from the axon terminal to the postsynaptic cell, triggering a response. Specific mechanism since it is directed only to cells with its specific synapse. o Acetylcholine: released by the neurons that trigger contraction of skeletal muscles.  Hormones: chemicals released from endocrine glands into the interstitial fluid, where they can then diffuse into the blood. Travels to the target cells, which can be distant. o Bloodstream distributes a hormone to virtually all cells of the body, but only cells possessing receptors specific for the hormone are able to respond. o Insulin: secreted by the pancreas and acts on target cells throughout the body to regulate energy metabolism. o Neurohormones: secreted by neurosecretory cells through a mechanism similar to that of neurotransmitter release. 5 CHEMICAL MESSENGERS o Vasopressin (ADH – antidiuretic hormone): neurohormone synthesized by neurosecretory cells originating in the hypothalamus. Once it is secreted from the acon terminlas in the posterior pituitary gland, it travels in the blood to its target cells (in the kidneys) effecting volume of urine excreted. CHEMICAL CLASSIFICATION OF MESSENGERS  Lipophilic (hydrophobic) molecules are lipid-soluble and, therefore, readily cross the plasma membrane, but they do not dissolve in water.  Lipophobic (hydrophilic) molecules are water-soluble and do not cross the plasma membrane.  AMINO ACID MESSENGERS: o Glutamate, aspartate, glycine, and gamma-aminobutyric acid (GABA). o Used in protein synthesis, but GABA belongs to a different class of amino acids. o Amino acids are hydrophilic, therefore they dissolve in water but not through plasma membranes. o They only function as neurotransmitters.  AMINE MESSENGERS: o Amines: chemical messengers derived form amino acids; possess an amine group (3NH ). o Catecholamines: contain a catechol group (6-C ring), and are derived from the amino acid tyrosine. Includes dopamine (neurotransmitters), norephinephrine (neurotransmitters), epinephrine (hormone). o Serotonin (derived from tryptophan), thyroid hormones (from tyrosine), histamine (from histidine). o Most are hydrophilic, except thyroid hormones (hydrophobic). They don’t dissolve in water, but they readily cross plasma membranes.  PEPTIDE/PROTEIN MESSENGERS o Chains of amino acids linked together by peptide bonds. Classified based on their sized. o Peptide: refers to chains fewer than 50 amino acids. Proteins: longer chains of amino acids. o They are hydrophilic.  STEROID MESSENGERS o Derived from cholesterol. Al body’s steroid messengers function as hormones. o They readily cross plasma membranes and are insoluble in water.  EICOSANOID MESSENGERS o Include a variety of paracrines that are produced by almost every cell in the body. o Derivatives of arachidonic acid (20-C fatty acid). o Readily cross the plasma membrane and are insoluble in water. o Prostaglandins, leukotrienes, and thromboxanes. SYNTHESIS AND RELEASE OF CHEMICAL MESSENGERS  AMINO ACIDS o Glutamate and aspartate are synthesized from glucose through a 3-step series of reactions. o Glucose is catabolized to pyruvic acid by glycolysis. Pyruvic acid is concerted to acetyl CoA, which then enters the Krebs cycle. Amine groups are added to the Krebs cycle intermediates to form glutamate or aspartate. o Glycine is synthesized from glycolytic intermediate, 3-phosphoglycerate, in a series of 4 reactions. o GABA is synthesized from glutamate in a single reaction catalyzed by enzyme glutamic acid decarboxylase. o Following their synthesis in the cytosol, amino acid neurotransmittes are transported into vesicles. Stored until it is released by exocytosis.  AMINES o All derived from amino acids. Thyroid hormones are synthesized in the cytosol by a series of enzyme- catalyzed reactions. o Dopamine is the precursor for norepiphrine, which leads to epinephrine. o Because dopamine is a precursor for the other catecholamines, all catecholamine-secreting cells possess the two enzymes that catalyze its synthesis: tyrosine b-hydroxylase and dopa decarboxylase. o Depending on which catecholamine it secretes, a cell may or may not possess enzymes for the remaining steps. o Those that secrete dopamine, lack the enzymes. Those that secrete norepinephrine and epinephrine contain dopamine b-hydroxylase. Those that secrete epinephrine contain phenylethanolamine N-methyl transferase (PNMT). 5 CHEMICAL MESSENGERS o After they are packaged into cytosolic vesicles, released when triggered (exocytosis).  PEPTIDES AND PROTEINS o Synthesized in the same way as other proteins for secretion. o Once translation starts, ribosomes attaches to the rough endoplasmic reticulum. Polypeptide is formed inside (prepropeptide). o In the lumen, proteolytic enzymes cleave off some amino acids from prepropeptide, yielding propeptide. o In the smooth ER, the propeptide is packaged into transport vesicles. o Vesicles transport the propeptide to the Golgi apparatus. o The propeptide is packaged into a secretory vesicles. Final product is a peptide. o Release occurs by exocytosis.  STEROIDS o Synthesized from cholesterol by enzymes located in the smooth ER or mitochondria. o Because they are m
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