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43 terms

Endocrinology Lecture 5

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How can you measure calcium?
Calcium can be measured using fluorescent Ca2+ selective chelators.
What are the advantages of fluorescent Ca2+ selective chelators?
Fluorescent Ca2+ selective chelators can shift wavelength and have a high signal to noise ratio
What are the disadvantages of fluorescent Ca2+ selective chelators?
Fluorescent Ca2+ selective chelators have to be loaded, have a subcellular distribution and require expensive imaging equipment
What happens when sperm enters an egg?
Point of sperm entry sends a wave of calcium ions
What are the resting levels of cytoplasmic calcium?
Resting levels of cytoplasmic calcium are very low, ~.1 microM
How is calcium signaling achieved?
Calcium signaling is achieved through release and reuptake of Ca2+, not from synthesis
Where is calcium stored?
Calcium is stored in internal membrane systems of the endoplasmic reticulum and mitochondria
What sequesters calcium?
Calcium is sequestered by calsequestrin and calreticulin
What is the large calcium release channel in the membrane of muscle sarcoplasmic reticulum?
The large calcium release channel in the membrane of muscle sarcoplasmic reticulum is the ryanodine receptor
What happens with calcium is released from sarcoplasmic reticulum to cytosol in skeletal and cardiac muscles?
Calcium is release causes muscle contraction
How many calcium ions does one calmodulin ion bind?
One calmodulin binds four calcium ions, two at each end
What does calmodulin do?
Calmodulin binds with calcium and interacts with other enzymes such as protein kinases and protein phosphatases
What is an example of a enzyme affected by calmodulin-Ca2+?
CaM-Kinase II is an enzyme that, alone, is inactive. When calmodulin/Ca2+ binds CaM-Kinase II, the CaM-Kinase II becomes activated. CaM-Kinase II then autophosphorylates and becomes fully active. Calmodulin and Ca2+ detach from phosphorylated CaM-Kinase II which is 50-80% active
How are bitter ligands transduced?
Bitter ligands bind to GPCRs and induce a PLC-IP3-DAG pathway
How are sweet ligands transduced?
Sweet ligands bind to GPCRs and induce a cAMP pathway that closes K+ channels and depolarizes the cell
What is the bitter ligand?
transducin
What is the sweet ligand?
gustducin
How are sour ligands transduced?
Sour ligands bind to ion channels and depolarize the cell
How are salty ligands transduced?
Salty ligands bind to ion channels and depolarize the cell
What are nociceptors?
Nociceptors is a sensory receptor that responds to potentially damaging stimuli causing the perception of pain
What binds capsaicin?
Capsaicin binds to vanilloid receptors or VR1, a ligand gated receptor that results in calcium influx into neurons and firing of action potentials
What does capsaicin do?
Capsaicin binds to vanilloid receptors and stimulates release of Substance P
What happens if you continue to eat capsaicin?
repeated use of capsaicin will deplete stores of substance P and limit pain transmission
What is substance P
Substance P is the main neurotransmitter for relaying pain
What is nitric oxide?
Nitrix oxide is a short lived paracrine hormone released by endothelial cells and relaxes smooth muscle
What forms nitric oxide?
Nitric oxide is formed from arginine by nitric oxide synthase (NOS)
What activates nitric oxide synthase?
Nitric oxide synthase is activated by calmodulin
What does nitric oxide activate?
Nitric oxide activates guanylyl cyclase which concerts GTP to cGMP
What does cyclic GMP do?
cGMP activates protein kinase G which phosphorylates a phosphorylase which dephosphorylates myosin light chain kinase which inhibits smooth muscle contraction
What is the effect of gas Nitric oxide?
Gas nitric oxide can pass through the plasma membrane and bind directly to guanyly cyclase
What are 7 inducers of NOS?
neurotransmitters (acetylcholine), cytokines (IFN-gamma), tumor necrosis factor alpha, salicylic acid, estrogen, nuclear factor kappa B, calcium
What are the 3 NOS isoforms?
nNOS (NOS I), iNOS (NOS II), eNOS (NOS III)
What is nNOS?
nNOS or NOS I is activated by nervous system Ca2+. It is 160kDa, constitutive, and involved in neurotransmission. Malfunctions in nNOS are involved in stroke, muscular dystrophy, ischemia-reperfusion injury
what is iNOS?
iNOS or NOS II is activated by inflammatory cells such as monocytes and macrophages. It is 130kDA, inducible, and involved in cytotoxicity. Malfunctions in iNOS are involved in septic shock and autoimmune disease
what is eNOS
eNOS or NOS III is activated by vascular endothelial cell Ca2+. It is 135 kDA, constitutive, and involved in vasodilation, anti platelet/leukocyte. Malfunctions in eNOS lead to endothelial dysfunction, atherosclerosis, hypertension
What NOS isoform is calcium independent?
iNOS is the calcium independent NOS isoform
What regulates iNOS?
iNOS is regulated by IL1, TNF, IFNgamma, LPS and mechanical strain
What regulates eNOS?
eNOS is regulated by calcium, estrogen, bradykinin, shear stress
What regulates nNOS?
nNOS is regulated by calcium, TNF
What are cyclic nucleotide PDEs?
Cyclic nucleotide PDEs or phosphodiesterases metabolize cAMP and cGMP. They are usually homodimers with at least 7 isoforms. There is 30-40% homology between families and conserved catalytic domains. They hydrolyze cyclic nucleotides at inactive 5' monophosphates
What PDE isoform is involved in impotence?
PDE V
What is sildenafil?
Sildenafil is Viagra, a phosphodiesterase 5 inhibitor
How does viagra work?
Viagra inhibitors phosphodiesterase 5. Then PDE5 cannot hydrolyze cGMP which is responsible for activation of protein kinase G which leads to smooth muscle relaxation