nerve/mm/cell communication Flashcards
what is endocrine signaling? example?
source of the signal is distant from the target, signal travels in blood, insulin
what is paracrine signaling?
cells release signals that affect neighboring cells
examples of paracrine signaling (2)
1- vascular endothelial cells secrete vasodilators and vasoconstrictors that act on the neighboring smooth muscle
2- tumor derived growth factors bind nearby epithelial cells to trigger blood vessel formation
what is juxtracrine signaling? example?
cells in very close proximity or direct contact, glial cells guiding axons during nervous system development
what is autocrine signaling?
cell responds to a signal that it has generated
what is an example of autocrine signaling?
stimulation of the EGFR receptor leads to increased levels of VEF, VEGF leaves the cell and binds to different receptors on the same cell
what is intracrine signaling? what type of receptor is required?
cell responds to a signal that it generated without the signal leaving the cell, intracellular receptor is required
what is an example of intracrine signaling?
estrogen-like molecules enter cell and encounter enzymes in the cell that change the molecules into signals that active receptors inside the cell
what are the 4 basic steps of signal transduction
signal released
signal binds receptor
transduction
response
what are ligand gated ion channels?
ligand binds to receptor causing a conformational change that opens or closes the ion channel
describe the GABA receptor
GABA is an inhibitory neurotransmitter, when GABA binds to GABA receptors, it opens Cl- channel, Cl- enters the cell and hyperpolarizes
describe IP3
IP3 binds IP3 channel on SER in smooth muscle, this allows Ca to leave SER and enter cytoplasm
describe RyR
RyR is on SER, when activated it causes release of Ca from RER to increase cytosolic Ca
describe K(ATP)
K(ATP) channel is inhibited when ATP binds, this leads to depolarization that allows for Ca release, that causes insulin release from b-cells
what is the neurotransmitter in skeletal muscle?
acetylcholine
what receptors do ACh bind on skeletal muscle?
nicotinic ACh receptors
describe what happens when ACh binds nicotinic receptors on skeletal muscle
ACh binds nicotinic receptors, this opens the Na channels in the receptor and Na flows into cell causing depolarization, wave of depolarization travels on membrane to T-tubule where it contacts DHP receptor, DHP receptor is activated and it activates RyR-1 receptor (which is physically linked) and RyR-1 opens to release Ca from SER, Ca binds to troponin-C allowing for the myosin-binding sites on actin to be exposed
3 general ways that signal termination occurs with ligand-gated ion channels
inactivation of receptors, inactivation of ion channels and membrane transporters (like SERCA)
describe the basic structure of a G-protein receptor
7 membrane spanning domains, g protein with 3 subunits (a,b,y)
describe general action of g-protein linked receptor
signal binds to G-protein receptor on membrane, G-protein receptor activated G-protein by GDP –> GTP, activated G-protein dissociates from receptor, a-GTP and By subunits dissociate, a-GTP and By subunits associate with effectors, a-catalyzed hydrolysis of GTP–>gdp inactivates a and promotes reassembly of aBy trimer
what is the neurotransmitter and receptor for GaS?
epinephrine and B-adrenergic receptor
explain the steps of GaS
epinephrine binds to B-adrenergic receptor
receptor is activated and it exchanges GDP–GTP to activate G-protein
G-protein interactions with adenylyl cyclase (effector)
activated adenylyl cyclase forms cAMP from ATP
increased cAMP levels activate protein kinase A
what is the “effector” in GaS?
adenylyl cyclase
what is the 2nd messenger in GaS?
cAMP
what is the action of protein kinase A?
phosphorylates serene and threonine residues on proteins to active the proteins
how is GaS terminated?
receptor inactivation by endocytosis, Gprotein inactivation, phosphodiesterase degradation of cAMP, phosphatase dephospho rylation of proteins
describe the effects of cholera toxin
causes constitutive activation of adenylyl cyclase to increase cAMP levels
describe the effects of pertussis toxin
inactivates the inhibitor of adenylyl cyclase to increase cAMP levels
what is the neurotransmitter and receptor for Gaq?
norepinephrine and a-adrenergic receptor
discuss the activity of Gaq
norepinephrine binds to a-adrenergic receptor
conversion of GDP to GTP activates G protein
activated G protein interacts with phospholipase C to activate it
activated phospholipase C will yield IP3 and diacyl glycerol
what is the consequence of increased IP3?
IP3 binds to IP3 receptors on the SER to increase cytosolic calcium
what is the consequence of increased diacyl glycerol?
diacyl glycerol activates protein kinase C
describe Ca and calmodulin
Calcium binds calmodulin to activate it
activated calmodulin can then activate a protein kinase
how is the Gaq signal terminated?
receptor inactivation, G protein inacgivation, degradation of IP3 or DAG, SERCA pumps or phosphatase mediated dephospho rylation of proteins
what ligands use nuclear receptors?
retinoic acid, bit D, steroids, thyroid hormone
how do intracellular receptors effect cells?
mainly by the alteration of transcript because ligands can directly bind DNA, this is slower than Gproteins
what is the action of tamoxifen?
SERM that occupies the estrogen binding site but does not stimulate proliferation
what are the 2 forms of guanylyl cyclase?
membrane bound “particulate” form
soluble form in cytosol
what is the function of guanylyl cyclase?
makes cGMP from GTP
what does cGMP regulate?
regulates smooth muscle tone and neurotransmission
what class of enzymes will inactivate cGMP?
phosphodiesterase
describe the MOA of viagra
viagra is a PDE-5 inhibitor, by inhibiting PDE-5, there are increased cGMP levels in cell, increased cGMP levels activate MLCP which causes relaxation in smooth muscle, relaxation results in vasodilation and erection
