Background[1-3]
Glycerophosphodiesterase phosphate domain 4 antibody is a type of polyclonal antibody that can specifically bind to the glycerophosphodiesterase phosphate domain 4 protein. It is mainly used for the in vitro detection of glycerol phosphodiesterase phosphate domain 4. detection.
Molecular cloning technology has revealed that phosphodiesterases (PDEs) are a large multi-gene family. The development of selective phosphodiesterase inhibitors will open up new ideas for the treatment of various diseases. PDEs is a large multi-gene family, which includes 11 types and a total of more than 30 kinds of phosphodiesterase isoenzymes with different substrate specificities, enzyme kinetic characteristics, regulatory characteristics, and different cellular and subcellular distribution areas. Similar structures, both contain regulatory and catalytic functional regions.
Glycerophosphodiesterase structure diagram
More than 75% of the amino acid sequences in the catalytic regions of various types of PDEs are identical. Shows homology among family members. And determines the specificity for substrate or inhibitor. PDEs have different substrate specificities: PDEs 4, 7, and 8 act exclusively on cAMP, while PDEs 5, 6, and 9 act selectively on cGMP. PDE3 binds to cAMP and cGMP with similar affinity, but hydrolyzes cGMP relatively poorly, so it is functionally regarded as specific for cAMP. cGMP acts as a negative regulator through competitive binding to the enzyme’s action site.
PDEs 1 and. 2 can hydrolyze both cAMP and cGMP, but PDE1 exerts different hydrolysis efficiencies on the two substrates due to its different subtypes. The amino-terminal regulatory regions of PDEs are highly heterogeneous, reflecting the different cofactors of PDE family members. This region is the binding site for calmodulin (CaM) (PDE1), non-catalytic cGMP (PDE2, 5, 6) and transducin (PDE6).
In addition, the amino-terminal parts of PDE3 and PDE4 also include target regions on the membrane, and PDE1, 3, 4, and 5 include protein kinase phosphorylation sites. These phosphorylation sites can regulate catalytic activity and/or subcellular localization. The specific combination of substrates and cofactors makes the interaction between cAMP and cGMP systems possible.
Apply[4][5]
For research on the regulation of cyclic nucleotide-dependent vasodilation by Rho kinase and phosphodiesterase
Currently, NO donors are widely used in the treatment of cardiovascular diseases, such as atherosclerosis, hypertension, coronary heart disease, etc. However, nitroglycerin tolerance that occurs during treatment greatly limits the clinical application of this drug.
Under certain pathophysiological conditions, the production of thromboxane (TxA2) increases. This substance activates the Rho/Rho kinase pathway through the TP receptor (thromboxane-prostanoid receptor), triggers calcium sensitization or inhibits NO production, causing Abnormal changes in blood vessel function. However, the impact of this abnormal change on cAMP-regulated vasodilation has not been reported.
Therefore, the bilateral common carotid arteries and thoracic aorta of rats were selected as the observation objects, and the vascular tension was measured using myograph and organ bath methods respectively; the primary cultured rat thoracic aorta was measured using laser confocal method. The intracellular nitric oxide and calcium ion concentrations in endothelial cells were measured; an ELISA kit was used to detect the levels of cyclic nucleotides in vascular tissue; and Western blotting was used to detect protein levels, aiming to observe: activation of TP receptors regulates cAMP The effects of endothelium-dependent and endothelium-independent vasodilation and explore the role of Rho kinase and PDE; the effect of the new PDE5 inhibitor T 0156 on nitroglycerin tolerance and whether the mechanism of action is related to increasing cGMP levels in vascular tissue.
