Tissues 11- Signalling between cells II Flashcards
Describe the signal transduction events in ionotropic receptors
Ligand binds to the receptor protien
Change in conformation of channel protein
pore opens allowing ions to move in or out
Example:
Acetylcholine acts on skeleal muscle causing contraction
GABAA
Located on many cells in the CNS
Allows transmission of anions
GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride ions
GABA acting on cells will cause a depression of activity
If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures
Describe g protiens
G-protein exists as a heterotrimer
Trimer = alpha, beta and gamma subunits (GDP is NOT part of the heterotrimer)
Beta and Gamma do NOT dissociate
G-protein coupled receptors are also known as serpentine receptors and 7-TM receptors (crosses the membrane 7 times - ‘7 transmembrane’)
Heterotrimer isn’t attached to the G-protein receptor to begin with
What are the Signal Transduction Events of g protien coupled receptors
Ligand binds and changes conformation of the receptor
G-protein heterotrimer binds to the internal compartment of the G-protein coupled receptor
GDP is exchanged for GTP
GTP provides energy for the alpha and beta-gamma subunits to dissociate
The subunits go and bind to their target proteins
Once the alpha subunit has attached to the target protein, internal GTPase activity within the subunit causes the GTP molecule to change to a GDP molecule
This allows the alpha subunit to unbind from the target protein and reform the heterotrimer with GDP attached
What are the 3 major forms of G-alpha subunits
Gs protein linked receptor
S = stimulatory
Stimulates adenylate cyclase
Adenylate cyclase converts ATP to cAMP
cAMP increases levels of PKA (protein kinase A)
EXAMPLE: b1-adrenergic receptor
NOTE: beta blockers act on the b1-adrenergic receptor
Gi protein linked receptor I = inhibitory Opposite effect to the Gs protein Inhibits adenylate cyclase thus reducing levels of cAMP and PKA EXAMPLE: M2-muscarinic receptor
Gq protein linked receptor Activates phospholipase C (PLC) PLC converts PIP2 ----> IP3 + DAG IP3 ---> increase in intracellular Ca2+ DAG - activates PKC EXAMPLE: AT-1 angiotensin receptor
Describe enzyme linked receptors
Ligand binds and the receptors cluster
Receptor clustering activates enzymes in the intracellular compartment
Enzymes and proteins are attracted to the receptor and move towards it to become activated
Activation of enzymes leads to phosphorylation of the receptor - which, in turn, leads to binding of signalling proteins to the cytoplasmic domain
Signalling proteins recruit other signalling proteins and a signal is generated within the cell
Tyrosine kinase phosphorylates any protein which has a tyrosine amino acid within it (a large proportion of the proteins within the cell)
The signal is terminated when a phosphatase removes the phosphate group
Three types of enzyme linked receptors
Tyrosine Kinase Linked Receptor (95%)
Guanylyl-cyclase Linked Receptor
Serine-Threonine Kinase Linked Receptor
Describe cytoplasmic intracellular receptors
Located within the cytoplasm
Attached to heat shock proteins
Ligands are usually STEROIDS which pass through the membrane and act on intracellular receptors
Ligand binds to the Type 1 receptor which dissociates from the heat shock protein
The ligand and receptor move together to the nucleus
It binds to the DNA and causes increased or decreased TRANSCRIPTION
These intracellular receptors are actually transcription factors
Effects of intracellular receptors take longer to occur
Describe nuclear receptors
Located within the nucleus and is already bound to DNA
Ligand comes in, moves through the nuclear envelope and binds to the receptor on the DNA causing changes in transcription
Two examples of intracellular receptors
Type 1 - Glucocorticoid Receptor
Ligand: cortisol, corticosterone
Physiological Effect: Downregulate immune response, increase gluconeogenesis
Agonists: Glucocorticoids
Type 2 - Thyroid Hormone Receptor
Ligand: Thyroxine (T4), Triiodothyronine (T3)
Physiological Effect: Growth & Development
Agonists: Thyroid hormones
