Inhibition of phosphatidylinositol kinase in vascular smooth muscle membranes by adenosine and related compounds.
Adenosine and 5'-chloro-5'-deoxyadenosine inhibited the phosphorylation of phosphatidylinositol in membranes prepared from aortic smooth muscle. The nucleosides did not affect the breakdown of phosphatidylinositol-4-phosphate. Under certain conditions, the membrane-bound phosphatidylinositol kinase phosphorylated exogenous phosphatidylinositol. The nucleosides inhibited the enzyme competitively with respect to magnesium-ATP and non-competitively with respect to phosphatidylinositol. Adenosine analogs modified in the ribose moiety were inhibitors with potencies comparable to that of adenosine, whereas adenine nucleotides and purine-modified adenosine analogs were much weaker inhibitors. Density gradient fractionation studies showed that phosphatidylinositol kinase is primarily associated with the sarcoplasmic reticulum. Vascular smooth muscle contraction is associated with increased phosphatidylinositol turnover. Inhibition of phosphatidylinositol kinase by intracellular adenosine may, therefore, be a factor involved in regulating vasodilation.
D019870:1-Phosphatidylinositol 4-Kinase; D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D017338:Cladribine; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010766:Phosphorylation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D014664:Vasodilation / Q000187:drug effects
D000227:Adenine Nucleotides; D003839:Deoxyadenosines; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D017338:Cladribine; C044739:5'-chloro-5'-deoxyadenosine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D000241:Adenosine