Ninja Nerd Physiology pharmacology topic 2

Overview of Receptor Pathways

  • The video aims to discuss various receptor pathways without covering all types for every hormone. It focuses on the most significant pathways.

Hormones Classification

Types of Hormones

  • Peptide Hormones

    • Water soluble
    • Hydrophilic amino acids facilitate interaction with water.
    • Examples: FSH (Follicle Stimulating Hormone), LH (Luteinizing Hormone), Growth Hormone, Glucagon, Parathyroid Hormone, Insulin, Oxytocin, ADH (Antidiuretic Hormone).

  • Steroid Hormones

    • Lipid soluble (derived from cholesterol).
    • Can penetrate cell membranes and often bind to intracellular receptors.
    • Examples: Testosterone, Estrogen, Progesterone, Aldosterone, Cortisol, Gonadocorticoids, Vitamin D, Thyroxine (acts like a steroid).

Mechanisms of Action

Peptide Hormones

  • Peptide hormones require receptors on the cell membrane because:
    • Size prevents them from penetrating the cell membrane.
    • The membrane is a phospholipid bilayer, which lipid-soluble molecules pass through.
  • They utilize second messenger systems to exert effects:
    • Focus on two major pathways: G stimulatory pathway and GQ pathway, and mention of G inhibitory pathway.
G Stimulatory Pathway

  1. Receptor Activation

    • Binding of peptide (e.g., epinephrine) to a G protein-coupled receptor (GPCR) changes receptor structure, activating the G stimulatory protein.
    • Initially bound to GDP - GDP is replaced with GTP, thus activating the protein.

  2. Action of G Stimulatory Protein

    • The active G protein (bound to GTP) interacts with adenylate cyclase (effector enzyme), also enhancing its activity.

  3. cAMP Production

    • Adenylate cyclase converts ATP to cyclic AMP (cAMP).

  4. Protein Kinase Activation

    • cAMP activates protein kinases (PK), which leads to phosphorylation of various proteins.
    • Definition of Kinase: An enzyme that adds phosphate groups (phosphorylation) to substrates is a critical regulatory mechanism.

  5. Biological Effects of Kinase Activation

    • Alter membrane permeability (e.g., ion channels).
    • Regulate metabolic pathways (e.g., glycolysis).
    • Influence transcription factors and cell proliferation, which can stimulate or inhibit responses based on context.
GQ Pathway

  1. Receptor Activation

    • Hormone (e.g., oxytocin) binding to a GQ protein-associated receptor alters its configuration, activating the GQ protein (GDP replaced by GTP).

  2. Activation of Phospholipase C

    • The GQ protein activates phospholipase C (PLC), which splits PIP2 (phosphatidylinositol 4,5-bisphosphate) into two second messengers - DAG (diacylglycerol) and IP3 (inositol trisphosphate).

  3. Function of DAG and IP3

    • DAG activates Protein Kinase C (PKC), allowing for protein phosphorylation similar to the stimulatory pathway.
    • IP3 promotes calcium release from the endoplasmic reticulum (ER) or sarcoplasmic reticulum (specific to muscle cells).

  4. Calcium's Biological Role

    • Calcium ions can bind to calmodulin, activating various kinases for cellular responses like muscle contraction or secretion.

Steroid Hormones

Mechanism of Action

  • Steroid hormones can easily diffuse through cell membranes due to their lipid solubility.
  • They bind to intracellular receptors (either cytosolic or intranuclear - often bound to heat shock proteins (HSP)).
  • Upon binding:
    • Heat shock proteins are displaced, activating the receptor.
    • The hormone-receptor complex binds to hormone response elements (HRE) on DNA, initiating transcription of target genes.
Result of Steroid Action
  • Gene activation can lead to:
    • Increased mitotic activity.
    • Protein synthesis related to metabolism, structure, or function.
    • Cell proliferation and growth.

Inhibition of Hormonal Action

  • Inhibition is achieved through specific enzymes:
    • Phosphodiesterase (PDE): Breaks down cAMP, preventing continuous stimulation of the pathways.
    • Can similarly act on pathways involving phospholipase mechanisms to prevent overactivation.

Conclusion

  • The video concluded with a summary of the G stimulatory pathways, GQ proteins, testosterone pathways, how peptide hormones interact with extracellular receptors, and the function of steroid hormones with intracellular receptors.
  • Further exploration of receptor pathways beyond those covered could be considered in more complex scenarios.