Lecture 3-Endocrine System Flashcards
Control of Smooth Muscle Cells
-a hormone may bind to various types of receptors
Ex: epinephrine. Binds to beta2 receptors in smooth muscle cells–> dilation of blood vessels. Also binds to alpha1 causes Ca2+ movement into cells–> muscle contraction–> blood vessel contractions
Smooth muscle cells beta/alpha receptors
- Beta receptors predominate in skeletal muscle and liver.
- Alpha receptors predominate in the viscera and smooth muscle
Phospholipids as Second Messengers
- PLC (enzyme) phopsholipase C- Inositol Phosphate system
- The effector is Phospholipase C (PLC)
- 3 messenger molecules are produced:
1. Diacylglycerol (DAG)
2. Inositol trisphosphate (IP3)
3. Ca 2+ ion
Regulation of PLC by GPCRs
- G protein is a “Gq” Type–> activation of PLC
- PLC originates IP3 and DAG from the inner membrane–> used as 2nd messengers
- IP3 activates release of Ca2+ from endoplasmic reticulum
- DAG and Ca2+ activates PKC, resulting in protein phosphorylation
G proteins and Ion Channels
OPENING OF Ca2+ Channels
-Binding of alpha subunit-GTP opens the Ca2+ channel
-increased Intracellular Ca2+ and released more Ca2+ from ER
-Ca2+ combines with calmodulin and activates protein kinases
OPENING OF K+ CHANNELS
-binding of beta/gamma subunits opens the inward rectifier K+ channel
-K+ leaves the cell
-Hyperpolarization of cells–> effect of acetylcholine
Specificity of G Protein-Coupled Receptor
- Receptor
-Types, location
2.G proteins
alpha subunit family=Gs,Gi,Gq (s=cAMP, i=cAMP, q=Level of Ca2+)
Beta gamma subunits (activate K+ channels) - Effector Systems–> 2nd messengers
-Adenylate cyclase–>cAMP
-Phospholipase C–> inositol phosphate
-Ion channels–> ions
Ligand (another specificity)
-Ligand is a molecule that binds to a receptor (not only GPCR)
EX: hormones(insulin), neurotransmitters (acetylcholine), Drugs (can be more selective)
-Types of Ligands
1.agonist-positive effect
2.anatonist-negative effect
3.partial antagonist-1/2 effect (somewhat inhibitory)
Factors important in ligand activity
- Relative numbers of receptors
- Types of receptors (receptors with positive or negative effects, tissue type)
What can happen to the receptors?
- These pathways are not only for GPCR
- Can be RECYCLED or CATABOLIZED (down-regulation)
- Down regulation allows you to decrease receptors, so you dont get too much hormone
Recycling of Receptors (Desensitization)
- Ligand-receptor complex goes inside the cell by ENDOcytosis
- Receptor and Ligand are internalized in vesicles called endosomes
- In recycling , the receptor goes back to the plasma membrane to be reused
Down-Regulation of Receptors: Mechanism
- Ligand-receptor endocytosis
- Receptor and Ligand are delivered to LYSOSOMES for degradation into smaller unites
- Degradation will lower the number of receptors on the plasma membrane
Receptor Tyrosine Kinase
- ONE single transmembrane protein, used for insulin, GH
- Kinase domain is in the cytoplasmic region
- Activated receptor undergoes a conformational change forming dimers
- Activation of the kinase domain–>autophosphorylation on tyrosine
- The kinase activity in the activated receptor phosphorylates intracellular targets (enzymes)–> activation or inactivation of target
Lipid-Soluble Hormone Mechanism: Intracellular Receptors
- Typical with steroids
- lipid-soluble hormones (steroids) bind to cytoplasmic (intracellular) or nuclear receptors
- Cytoplasmic (Glucocorticoid) and nuclear(estrogen, T3,T4)
