Altered turnover of polyphosphoinositides in the erythrocyte membrane of the spontaneously hypertensive rat.
The metabolism of inositol phospholipids of the erythrocyte membrane was compared in normotensive Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone SHR (SHR-SP) rats. This was performed on isolated ghost membranes by measuring the incorporation of 32P from [ gamma-32P ] adenosine triphosphate (ATP) into the diphosphoinositides (DPI) and the triphosphoinositides (TPI) which were the only 32P-labeled phospholipids. 32P-labeling of TPI was altered in adult and 3-week-old SHR as well as in SHR-SP compared to WKY controls; the radioactivity associated with TPI in hypertensive rats was about 30% lower than that associated with TPI in age-matched normotensive controls. By contrast, the radioactivity associated with DPI was similar in both hypertensive and normotensive rats. Measurement of the phosphoinositide distribution in both SHR and WKY indicates that the change observed in 32P-TPI could not be accounted for by a reduced phosphatidylinositol content in SHR membrane. Measurement of the Mg2+-activated TPI-phosphomonoesterase and of the Ca2+-activated polyphosphoinositide phosphodiesterase activities did not show any significant difference between SHR and WKY. It thus appears that the altered phosphoinositide metabolism observed in hypertensive rats was a consequence of some alteration in the activity of kinases which are responsible for the conversion of phosphatidylinositol into DPI and TPI. These results also suggest that the defect in phosphoinositide metabolism observed in genetically hypertensive rats was not a consequence of the blood pressure elevation and could be related to the pathogenesis of hypertension.
D000818:Animals; D002118:Calcium / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006973:Hypertension / Q000097:blood*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D010743:Phospholipids / Q000302:isolation & purification; D010744:Phosphoric Monoester Hydrolases / Q000097:blood; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; C035215:inositol triphosphate phosphomonoesterase; D010744:Phosphoric Monoester Hydrolases; D008274:Magnesium; D002118:Calcium