1. Chemical messengers

2. Outline • Mechanisms of intercellular communication • Chemical messengers • Signal transduction mechanisms

3. Direct through gap junctions Cells exchange chemicals through connections between cytoplasm Indirect through chemical messengers The messenger must bind to a matching receptor and stimulate a response Mechanisms of intercellular communication

4. Autocrine: the cell secretes a chemical which can bind on its own membrane and stimulates a response Paracrine: a cell secretes a chemical which can bind to a receptor on a neighboring cell  trigger a response Hormone: a chemical travels long distance through the blood before binding to its own target organ and stimulating a response Neurotransmitter: influences a distant organ by secreting chemicals which travel through axons Indirect messengers Figure 5.1a

5. Chemical classification of messengers • Lipophilic molecules = lipid soluble  can cross the phospholipid bilayer  cannot be stored by the cell  synthesized and released immediately. ex: steroids (from cholesterol), eicosanoids (from fatty-acids) • Lipophobic molecules = not soluble in lipid  cannot cross the phospholipid bilayer  can be stored in vesicles by the cell. ex: amino acids, peptides, proteins

6. For autocrines, paracrines and neurotransmitters: diffusion For non-water soluble hormones: transport into in the blood bound to carrier proteins for transport (steroids and thyroid hormones) Hormones will eventually be degraded by the liver and eliminated by the kidneys  each has a characteristic ½ life. Transport and elimination

7. The hormones must bind to a matching receptor The binding is specific for this hormone  receptor affinity (a receptor might have differing affinity for various hormones (ex: epinephrine and norepinephrine) Hormone binding

8. - steroid hormone: cross the phospholipid bilayer  receptors are inside the cytoplasm or nucleus  activates transcription and synthesis of new proteins response slow but sustained - Lipophobic hormones bind to receptors located on the surface of the cell membrane  activates a cascade of enzymes  response amplified  rapid response but not sustained Signal transduction: the binding of the hormone to its receptor triggers a cell response

9. The binding of the hormone to its receptor can trigger the opening of a channel, induce enzymatic activation Mechanisms of transduction (do not memorize these mechanisms

10. Cholera Application

11. Readings • Chp. 5, p. 126-145. • Discovery: p.128, • Clinical connections: p. 140. • Not expected to be known: • Clinical connections: p. 134