Principles of Human Physiology

Learning Outcomes

• Compare the three major functional classes of chemical messengers: Paracrines, neurotransmitters, and hormones.

  • Discuss the type of cell that releases each messenger.

  • Explain the pathways for messengers to get to target cells.

• Describe the basic structure and function of messenger classes: amines, catecholamines, peptides, steroids, and eicosanoids. Discuss mechanisms of synthesis, release, transport, and signal transduction.

• Compare signal transduction mechanisms:

  • Distinguish between lipophilic and lipophobic messengers and their effects on target cells.

5.1 Mechanisms of Intercellular Communication

General Mechanisms

• Direct Communication:

  • Gap Junctions: Specialized intercellular channels that allow for direct signaling between adjacent cells.

• Indirect Communication:

  • Chemical Messengers: Involves signaling molecules and their receptors.

Direct Communication through Gap Junctions

• Connexons:

  • Composed of connexin integral proteins that form channels between cells for direct communication.

  • Particle Movement Acts as a Signal: Movement of small molecules such as ions or metabolites directly through gap junctions.

  • Commonly observed in smooth muscle and cardiac muscle tissues.

Indirect Communication through Chemical Messengers

• Chemical Messenger Components: Consist of a ligand (the signaling molecule) and a receptor (the binding site on the target cell).

• Pathway of Indirect Communication:

  • Signal travels from a secretory cell to the interstitial fluid (ISF) and then to the target cell.

  • Initiates signal transduction, resulting in a cellular response.

5.2 Chemical Messengers

Classification by Function

• Local Action:

  • Paracrine and Autocrine Chemical Messengers.

  • Pathway: Secretory cell → ISF → Target cell.

  • Examples: Growth factors, clotting factors, immune system cytokines, and nitric oxide (NO).

Local Action but Long-Distance Communication

• Neurotransmitters: Communication between a presynaptic cell and a postsynaptic cell over a synaptic gap (ISF), targeting neurons, glands, and muscle cells.

Long-Distance Communication

• Hormones:

  • Pathway: Endocrine cells → ISF → Blood → ISF → Target cell.

  • Examples: Insulin, estrogen, thyroxin.

• Neurohormones: Similar to hormones but released from neurons.

  • Pathway: Neuron → ISF → Blood → ISF → Target cell.

  • Examples: Antidiuretic hormone (ADH), oxytocin.

Table 5.1: Functional Classification of Chemical Messengers

• Classes of Messengers:

  • Paracrine: Short distance, diffuses through ISF.

  • Neurotransmitter: Diffusion across synaptic cleft.

  • Hormone: Long distance through blood.

• Transport Modes:

  • Paracrine: Diffusion.

  • Neurotransmitter: Diffusion.

  • Hormones: Transported via blood.

• Chemical Classification (Examples provided):

  • Paracrine: Amines, peptides/proteins, eicosanoids.

  • Neurotransmitters: Amino acids, amines, peptides/proteins.

  • Hormones: Amines, steroids, peptides/proteins.

Chemical Classification of Messengers

Solubility Properties

• Hydrophilic/Lipophobic Ligands:

  • Bind to receptors on the cell membrane.

  • General Target Cell Response: Enzyme activation and changes in membrane permeability.

• Hydrophobic/Lipophilic Ligands:

  • Usually have receptors located intracellularly.

  • General Target Response: Gene activation.

Amino Acids

• Solubility: Hydrophilic or lipophobic.

• Expected Location of Receptors: Cell membrane.

• Function: Only four amino acids (discussed in Chapter 2) act as messengers.

  • Examples: Glutamate, aspartate, glycine, GABA.

Synthesis and Release Characteristics of Amino Acids

• Function: Used exclusively as neurotransmitters.

• Synthesis: Occurs within the neuron.

• Storage: Contained in secretory vesicles.

• Release Mechanism: By exocytosis.

Amines

• General Information: Most are hydrophilic/lipophobic, with the exception of thyroid hormones.

• Origin: Derived from amino acids, leading to various functions.

• Examples:

  • Catecholamines: Derived from tyrosine.

  • Subtypes: Dopamine, norepinephrine, epinephrine.

  • Thyroid Hormones: Derived from two tyrosine amino acids.

  • Histamine: Derived from histidine.

  • Serotonin: Derived from tryptophan.

Synthesis and Release Characteristics of Amines

• Production: In the cytosol of the secreting cell.

• Storage: Found in secretory vesicles for release.

• Release Mechanism: Released by exocytosis; the specific amine produced depends on the enzymes present in the secreting cell.

Synthesis Pathway of Catecholamines

• Pathway:

  • Tyrosine → L-dopa → Dopamine (DA) → Norepinephrine (NE) → Epinephrine (E).

  • Serotonin: Derived from tryptophan.

  • Histamine: Derived from histidine.

Peptide and Protein Messengers

• General Characteristics: Most abundant type of ligand; hydrophilic/lipophobic.

• Receptor Location: Typically found on plasma membrane due to their solubility properties.

• Structure:

  • Peptide Ligand: Less than 50 amino acids.

  • Protein Ligand: Greater than 50 amino acids.

• Variety of Functions: Extensive roles in signaling pathways.

Synthesis and Release Characteristics of Peptides & Proteins

• Formation: Involves cleaving larger protein chains.

• Storage: Stored in secretory vesicles until release is triggered.

• Release Mechanism: Released via exocytosis, undergoing general terminology in the process.

Steroid Hormones

• Characteristics: Hydrophobic/lipophilic; derived from cholesterol.

• Examples: Include progesterone, estriol, dihydrotestosterone, cortisol, and aldosterone.

• Synthesis and Release Characteristics:

  • Synthesis: Occurs on demand within smooth endoplasmic reticulum (ER).

  • Membrane Permeability: Can diffuse through membranes, unable to be stored in vesicles due to lipid solubility.

Eicosanoid Ligands

• General Properties: Hydrophobic/lipophilic substances.

• Receptor Location: Cell membrane; predominantly paracrine agents.

• Synthesis: Derived from arachidonic acid, a component of cell membrane phospholipids.

• Examples: Prostaglandins, leukotrienes, thromboxanes.

• Major Synthetic Pathways:

  • Cyclooxygenase pathway

  • Lipoxygenase pathway.

Table 5.2: Chemical Classification of Messengers

• Classes and Properties:

  • Amino Acids: Lipophobic, receptor on plasma membrane, functions as neurotransmitters.

  • Amines: Lipophobic (most), receptor on plasma membrane, functions as paracrines, neurotransmitters, hormones.

  • Peptides/Proteins: Lipophobic, receptor on plasma membrane, functions as paracrines, neurotransmitters, hormones.

  • Steroids: Lipophilic, receptors located in cytosol, function as hormones.

  • Eicosanoids: Lipophilic, receptors mostly on plasma membrane, function as paracrines.

Transport of Messengers

Diffusion Through Interstitial Fluid

• Description: Used when the source and target cells are in close proximity.

• Characteristics: Ligands are generally short-lived due to rapid degradation.

• Examples: Paracrines, autocrines, neurotransmitters, and many cytokines.

Blood Transport

• Description: Necessary when target cells are at significant distances from the source.

• Properties: Hydrophilic (lipophobic) ligands dissolve directly in plasma, while hydrophobic (lipophilic) ligands bind to carrier proteins for transport.

• Examples: Hormones, neurohormones, some cytokines.

Messenger Half-Life

• Definition: The time taken for a chemical's concentration to decrease by half.

  • Series Example: Initial concentration of 1 → 0.5 → 0.25.

• Sources of Degradation: The liver manages degradation, while the kidneys are responsible for excretion.

• Types of Messengers:

  • Dissolved or Free Messengers: Subject to rapid degradation; relatively shorter half-life.

  • Example: Half-life of insulin is less than 10 minutes.

  • Carrier Bound Messengers: Protected from degradation; typically have a longer half-life.

  • Example: Half-life of cortisol is 90 minutes.