Chemical Messengers and Gap Junctions

Chemical Messengers

• Intercellular communication occurs through direct and indirect mechanisms
• Direct communication involves gap junctions, allowing ions and small molecules to pass between adjacent cells
• Indirect communication utilizes chemical messengers
• Chemical messengers are produced by a source cell, released, travel to a target cell, and bind to receptors on the target cell, triggering a cellular response. This process is indirect.

Gap Junctions

• Gap junctions are composed of membrane proteins
• They link the cytosol of two adjacent cells
• Particle movement between cells is a signal
• Communication is direct
• Common in smooth and cardiac muscle

Chemical Messenger Classification

• Classification by function (paracrine, autocrine, neurotransmitter, hormone, neurohormone)
• Classification by chemical properties (solubility—water soluble/lipid soluble; chemical class—amino acids, amines, peptides/proteins, steroids, eicosanoids)

Functional Classification of chemical messengers

• Paracrine: Short distance signaling between nearby cells. Example: histamine for inflammation response
• Autocrine: Same as paracrine but the chemical signals the same cell which secreted it.
• Neurotransmitter: Produced by neurons, released into the extracellular fluid (ECF) of the synaptic cleft. Examples: acetylcholine, GABA, serotonin.
• Hormone: Produced by endocrine cells, secreted into blood via interstitial fluid. Examples: insulin, estrogen, thyroxine
• Neurohormone: Special class of hormone produced by neurons, secreted into the blood. Examples: antidiuretic hormone (ADH), oxytocin

Chemical Classification of Messengers

• Lipophobic: Water soluble; not lipid-soluble, do not cross the cell membrane. Receptors are on the cell membrane.
  • General action of target response is enzyme activation and membrane permeability changes.
• Lipophilic: Lipid-soluble; not water-soluble, easily cross the cell membrane. Receptors are usually intracellular. General action of target response is via gene activation.

Amino Acids

• Made from glucose (Glutamate, aspartate, and Glycine) and 3-phosphoglycerate (GABA)
• Lipophobic
• Target cell receptors on the cell membrane.
• Examples: glutamate, aspartate, glycine, GABA (all function as neurotransmitters)

Amines

• Most are lipophobic, except thyroid hormones.
• Receptor targets are on the cell membrane.
• Made or derived from an amino acid.
• Contain an amine group (chemical structure).
  • Catecholamines (from tyrosine): dopamine, norepinephrine, epinephrine
  • Thyroid hormones (from two tyrosine amino acids)
  • Histamine (from histidine)
  • Serotonin (from tryptophan)

Peptide and Protein Messengers

• Most abundant type of ligand
• Lipophobic
• Target receptors on the cell membrane
• Made of chains of amino acids
• Peptide ligand (<50 amino acids)
• Protein ligand (>50 amino acids)

Steroids

• Lipophilic
• Derived from cholesterol
• All steroid messengers function as hormones

Eicosanoids

• Lipophilic
• Intracellular target receptors
• Most are derived from arachidonic acid (a cell membrane phospholipid)
• Synthesized on demand
• Cyclooxygenase and lipoxygenase pathways

Synthesis and Release of Chemical Messengers

• Lipophobic Ligands: Synthesized on demand, released immediately from source, rate depends on synthesis
• Lipophilic Ligands: Synthesis is independent of demand, stored in vesicles until needed, released by exocytosis; rate is determined by exocytosis.

Transport of Chemical Messengers

• Diffusion: Ligands diffuse through interstitial fluid, source and target are close (paracrines, neurotransmitters, most cytokines).
• Bloodborne: Lipophobic ligands dissolve in plasma, lipophilic ligands bind to carrier proteins in blood.

Messenger Transport and Half-Life

• Messenger half-life: Time for concentration to decrease by half in blood or interstitial fluid.
• Messengers dissolved in plasma have a relatively short half-life (example: insulin <10 minutes).
• Messengers bound to plasma proteins have a relatively long half-life (example: cortisol 90 minutes).

Signal Transduction (overview)

• Messenger binds to receptor, resulting in a cell response.
• Signal transduction: process of producing a response in the target.
  • Two forms of target response: movement of ions or phosphorylation of enzymes.

Receptor Binding

• Specificity (one messenger can bind to multiple receptors)
• Binding is brief and reversible.
• Affinity: strength of the binding
• Location: Lipophobic ligands bind to receptors on the cell membrane, lipophilic ligands bind intracellularly.

Receptor Properties

• Specificity: one messenger may bind to many receptor types, one target cell can have multiple receptor types
• Number of receptors per cell varies and is dynamic (up-regulation and down-regulation)

Up-regulation/Down-regulation

• Up-regulation: receptor number increases on target
• May result from too little messenger, increasing sensitivity
• Down-regulation: receptor number decreases on target
• May result from excess messenger, decreasing sensitivity, tolerance develops

Agonists and Antagonists

• Agonist: Chemical mimics normal receptor response
• Antagonist: Chemical binds to receptor but does not trigger a response; competes with normal ligand; response is opposite to agonist action.

Intracellular-Mediated Response

• Typical for lipophilic ligands (except thyroid hormones).
• Receptors are found in the cytosol or nucleus.
• Cell response occurs via gene activation.

Signal Transduction by Membrane-Bound Receptors

• Two forms of target response: movement of ions; phosphorylation of enzymes
• Overview of mechanisms: channel-linked, enzyme-linked, and G protein-coupled receptors (GPCRs).

Channel-Linked Receptors

• Fast ligand-gated channels
• Receptor and channel are the same protein
• Direct action: Binding opens/closes channel, causing ion movement, triggering target response

Enzyme-linked Receptors

• Receptor and enzyme are the same protein
• Direct action: Ligand binding activates enzyme, causing target response
• Examples: tyrosine kinases and guanylate cyclases.

G Protein-Coupled Receptors (GPCRs)

• Receptors and channels are different proteins, linked by G proteins
• Receptors, not ligands, bind to G protein nucleotides
• Signal transduction is indirect (multiple steps)

Second Messenger Systems

• Triggered by the first messenger (ligand)-activates the G protein-coupled receptor
• The receptor activates the G protein
• The G protein activates the amplifier enzyme
• The amplifier enzyme activates second messenger production.
• Second Messengers include cAMP, cGMP, IP3, DAG, and calcium ions

Endocrine and Nervous Communication

• Endocrine Communication: Target cell secrets hormone, enters blood; blood spans the distance to the target; communication is slow but prolonged.
• Nervous Communication: Nerve cells transmit signals within and between cells through long axons and synapses; faster communication, but shorter duration.

Overall notes:

• The information presented here summarizes the content of the provided lecture notes on chemical messengers, their mechanisms of action, and signal transduction within the human body. Multiple figures and tables are included to illustrate the concepts. Tables list examples of various messengers and their associated mechanisms. There is a comprehensive breakdown of the types of messengers and their corresponding responses within the body.

Explore the fascinating world of chemical messengers and gap junctions with this quiz. Test your knowledge on the mechanisms of intercellular communication, their classifications, and the roles they play in cellular responses. Perfect for students of biology or anyone interested in cellular processes.