1. Chemical messengers

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

3. Mechanisms of intercellular communication 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

4. Figure 5.1a Indirect messengers 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

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. Transport and elimination 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.

7. Hormone binding 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)

8. Signal transduction: the binding of the hormone to its receptor triggers a cell response - 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

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

10. Application Cholera

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