Chemical Messengers

1. Chemical Messengers

2. Mechanism of intracellular communication • Direct: Cells are physically linked by gap junctions (few instances). • Indirect: Cells communicate through chemical messengers (most instances).

3. Gap junctions • Gap Junctions are formed by plasma membrane proteins, (called connexins) that form the structures, (called connexons) that form channels for ions and small molecules. • The movement of small molecules through gap junctions metabolically couples the cells and causes cells of organs to act as a unit.

4. Chemical messengers • Ligands (from secretory cell) are secreted in the interstitial fluid  target cells respond by receptors that bind the messenger  signal transduction. • More receptors + messengers  stronger cell response.

5. Functional classification

6. 1) Paracrines • Paracrines: communicate with neighboring cells. • Some paracrines: Growth factors – Clotting factors – cytokines. • Ex: Histamine: is secreted by mast cells scattered throughout the body during allergic reaction or response to Bacterial Infection Inflammation.

7. Inflammation • Redness: Increase of blood flow. • Swelling: leakage of fluid out of blood vessels into the affected tissues. 

8. 2) Autocrines • Act on the same cell. (secretory cell = target cell). • Often function as paracrines and regulate their own secretion.

9. 3) Neurotransmitters • Neurotransmitters are released from neurons, specialized portion called axon terminal. Very close to the target cell. • Synapse: is the junction between two cells. • Synaptic signaling: is the communication by neurotransmitters. • Presynaptic neuron: is the cell releasing the neurotransmitter. • Postsynaptic neuron: is the target cell ( another neuron, gland cell, muscle cell). • Ex: Acetycholine : causes contraction of skeletal muscles.

10. 4) Hormones • Hormones: are released from endocrine glands and diffuse into the blood, then travel to their target cells which possess receptors specific for the hormones. • Ex: Insulin is secreted by pancreas and regulates energy metabolism.

11. Neurohormones • Neurohormones, are released by a special class of neurons (neurosecretory cells) and diffuse into the blood. • Ex. Vasopressin = (ADH = antidiuretic hormone) is synthesized in the hypothalamus (brain in the posterior pituitary gland) and travels to target cells in the kidneys to regulate excretion of urine.

12. !Note • One chemical messenger may fit more than one functional class. • Ex: Serotonin is a neurotransmitter when released from neurons. But it is a paracrine when released from platelets.

13. Chemical Classification • Chemical structuredetermines: (Synthesis. Release. Transport. Signal transduction). • Messengers dissolving in water = lipophobic = hydrophilic = don't cross the plasma membrane. • Messengers which cross the lipid bilayer in the plasma membrane = (lipophilic= lipid-soluble) = hydrophobic.

14. Chemical Classification 1) Amino Acids: 2) Amines: lipohobic except  thyroid hormones are lipophilic + receptors in the nucleus of target cells. 3) Peptides / Proteins. 4) Steroids. 5) Eicosanoids. 6) Others: Acetylcoline + Nitric Oxide.

15. 1)Amino acids • Amino Acids (NH2-RCOOH): are the Neurotransmitters in the brain and spinal cord. • Glutamate, Aspartate and Glycine: are alpha Aa used in protein synthesis. • Gamma – aminobutyric acid (GABA). • Amino acids are lipophobic. 

16. 2)Amines • Amines (R – NH2 ): 1) Catecholamines: contain catechol group = a six-carbon ring, derived from tyrosine Aa. and include: • Dopamine – norepinephrine: (function as neurotransmitters) • epinephrine: (functions as a hormone). 2) Serotonin = neurotransmitter derived from tryptophan. 3) Thyroid hormones = neurotransmitter derived from tyrosine. 4) Paracrinehistamine = neurotransmitter derived from histidine. 5) Amines are lipophobic: except Thyroid hormones (Amines but lipophilic)

17. 3)Peptides / Proteines • Peptide (protein) messengers: 2 ~ > 100 Aa. • (peptide =< 50 Aa) • (protein => 50 Aa). • They are lipophobic.

18. 4) Steroid messengers • Derived from cholesterol. • Lipophilic / insoluble in water / cross plasma membrane. • Steroids can not be stored but synthesized on demand and released immediately.

19. 5) Eicosanoids • Eicosanoids are : -Prostaglandins -Leukotrienes -Thromboxanes • Eicosanoids are lipophilic.

20. Transport of messengers • Simple diffusion to reach the near target cells. • Dissolution in blood to reach far place. • Carrier proteins for hydrophobic molecules.

21. Carrier proteins • Some carriers are specific for a particular hormone. Ex: corticosteroid-binding globulin which transport the hormone ;cortisol. • Other carriers transport many hormones. Ex: albumine. • Hormones with carriers have longer half-life than dissoluble forms.

22. Signal Transduction Mechanism by intracellular receptors • The complex hormone-receptor binds certain region of DNA called the Hormone response element (HRE), which is the beginning of a specific gene. • Then, the gene is activated or deactivated. • If activated, mRNA is transcribed and moves to cytosol. • mRNA is translated to proteins by ribosomes.

23. Signal Transduction Mechanismby Membrane-Bound Receptors • The receptors for lipophobicmesengers fall into three categories: • Channel-linked receptors. • Enzyme-linked receptors. • G-protein receptors.

24. Channel-Linked Receptors • They are specific for some ions and regulated between open and closed states. • They fall into 2 categories: • Fast channels, in which the receptor and the channel are the same protein. • Slow channels, the receptor and the channel are separate proteins but coupled by a third protein called, G protein.

25. Calcium Ion-channel • Calcium channels when open, calcium enters the cell as second messenger and binds a protein called calmodulin. • The complex activates a protein kinase which phosphorylates other proteins to work.

26. Enzyme-Liked Receptors • They are trans-membrane proteins with the receptor side facing the interstitial fluid and the enzyme side facing the cytosol. • Most of them are tyrosine kinases, which phosphorylate the amino acid tyrosine in certain locations in target proteins.

27. G protein-Linked Receptors • They activate specific membrane proteins called G protein. • Activated G proteins can activate or inhibit intracellular proteins. • Many of them activate the formation of second messengers:1) cAMP mainly, 2) cGMP, 3) inositol triphosphate(IP3), 4) diacyl-glycerol(DAG), and 5) calcium.

28. Nervous system and Endocrine system • Responses triggered by neural signals are generally fast and brief. • Responses by Endocrine system are slow and long lasting. • Neurons send signals to specific target cells which are connected to by synapses. • Endocrine system broadcasts signals to target cells throughout the body.