Chemical Messengers – Quick Reference

Gap Junctions

  • Direct cell-to-cell communication via gap junctions.

  • Connexons form channels allowing passage of small molecules between neighboring cells.

  • Enables rapid, bidirectional signaling.

Communication via Chemical Messengers

  • Secretory cell releases chemical messenger; target cell responds via receptors.

  • Messenger types include paracrines, neurotransmitters, and hormones.

Paracrines

  • Secretory cell acts on neighboring target cell.

  • Receptor on adjacent cell; limited to local environment.

Neurotransmitters

  • Secretory cell is a presynaptic neuron.

  • Released into synapse; binds receptors on postsynaptic target.

Hormones

  • Secreted by endocrine cells into the bloodstream.

  • Reach distant target cells with receptors.

  • Some cells lack receptors and do not respond.

Catecholamines

  • Biosynthesis pathway:

    • Tyrosine → L-DOPA → Dopamine → Norepinephrine → Epinephrine

  • Key enzymes: tyrosine hydroxylase, dopa decarboxylase, dopamine β-hydroxylase, PNMT.

  • Stored in vesicles for exocytotic release.

Peptide Synthesis and Hormone Synthesis

  • Peptide synthesis:

    • Translation on rough ER as prepropeptide → propeptide → cleaved to active peptide.

    • Transport through Golgi to secretory vesicles; released by exocytosis.

  • Example: parathyroid hormone synthesis pathway (preprohormone → prohormone → hormone).

Steroid Hormones

  • Derived from cholesterol; lipophilic.

  • Include progesterone, corticosterone, cortisol, aldosterone, androgens, estrogens.

  • Travel in blood largely bound to carrier proteins; diffuse across membranes to intracellular receptors.

Eicosanoids Synthesis

  • From membrane phospholipids via arachidonic acid.

  • Pathways:

    • Cyclooxygenase pathway → prostaglandins, prostacyclins, thromboxanes.

    • Lipoxygenase pathway → leukotrienes.

Hydrophilic Messengers

  • Hydrophilic messengers secreted by exocytosis.

  • Dissolve in blood; act on surface (extracellular) receptors.

Hydrophobic Messengers

  • Hydrophobic messengers secreted by diffusion.

  • Mostly bound to carrier proteins in blood (>99%); a small free fraction (<1%) is active.

  • Diffuse across membranes to intracellular receptors.

Receptor Specificity

  • Target cells have specific receptors for each messenger.

  • Messenger-receptor binding triggers cellular response.

  • A cell may express multiple receptor types for different messengers.

Messenger Concentration and Affinity

  • Receptor occupancy depends on messenger concentration and receptor affinity.

  • Higher concentration increases binding; higher affinity increases binding at lower concentrations.

Lipophilic Hormone Effects on Target Cells

  • Diffuse across the plasma membrane.

  • Bind cytosolic or nuclear receptors.

  • Hormone-receptor complex modulates gene transcription via DNA elements (e.g., hormone response elements).

  • Leads to changes in protein synthesis and cellular function.

Mechanism of Steroid Action

  • Steroid hormone binds intracellular receptor; receptor often forms a dimer.

  • Complex binds DNA at hormone response elements; alters transcription of target genes.

  • Result: new protein synthesis and cellular responses.

Channel-Linked Receptor

  • Ligand-gated ion channels.

  • Binding opens the channel, allowing ions (Na⁺, K⁺, Cl⁻) to pass.

  • Rapid changes in membrane potential and cellular activity.

Calcium Channel (Second Messenger) Example

  • Calcium channels open in response to signaling; Ca²⁺ enters cytosol.

  • Ca²⁺ binds calmodulin; activates kinases and other enzymes.

  • Outcomes: altered secretion, metabolism, or contraction.

Enzyme-Linked Receptors

  • Receptor tyrosine kinases (RTKs) or related enzymes.

  • Ligand binding induces receptor dimerization and receptor phosphorylation.

  • Phosphorylation triggers intracellular signaling cascades affecting metabolism and gene expression.

G Protein Signaling

  • Receptors activate heterotrimeric G proteins.

  • GDP → GTP on the Gα subunit; Gα and/or Gβγ modulate downstream effectors.

  • Leads to changes in cellular activity via second messengers (e.g., cAMP, IP₃, DAG).

Signal Transmission in Neurons

  • Two modes: electrical transmission along axons; chemical transmission at synapses.

  • Neurotransmitter release at synapse binds receptors on the postsynaptic cell to elicit response.