Inositol phospholipid metabolism in the kidney.
The unique features of renal phosphoinositide metabolism include an increase in tissue phosphoinositide levels induced by PTH. The significance of this finding remains unclear. Another unusual finding is the localization of phospholipase C activity in a BBMV preparation. As suggested in the review, the transducing mechanism involving cleavage of phosphoinositides by a phospholipase C would be expected to include a close association between phospholipase C and the plasma membrane. However, few attempts to localize phospholipase C activity in the plasma membrane have succeeded. The kidney also plays an unusual role in inositol metabolism in that it is the only organ that significantly catabolizes inositol. The kidneys also synthesize inositol. There is an enormous concentration of inositol in the outer medulla. This coexistence of significant inositol synthesis, breakdown, and the presence of extremely high amounts of free inositol is an intriguing but unexplained phenomenon. The substantial rate of endogenous renal inositol synthesis does not, however, preclude inositol deficiency states. There is a deficiency of inositol in diabetic peripheral nerve and in glomeruli isolated from diabetic rats. Such deficiencies may arise from a disturbance in the balance of synthesis, breakdown, and excretion of inositol, and particularly from the competition of glucose with the inositol transporter in the proximal tubule. Future studies of renal phosphoinositide metabolism need to address both basic cell biological questions and broader physiological or functional questions. The more basic issues include the question of which phosphoinositide is being attacked by agonist-stimulated phospholipase C. That is, are all the events explained by hydrolysis of PtdIns(4,5)P2, or are the other phosphoinositides hydrolyzed as well? Also, it would appear that stimulated phosphoinositide metabolism occurs quite early following receptor occupation, but there is still no way of selectively blocking stimulated phosphoinositide metabolism to see if it is a necessary first step in a cascade of events leading to cell response. Thus, the relationship of stimulated phosphoinositide metabolism to cell functions remains incompletely understood. At least two cellular functional or biochemical changes associated with stimulated phosphoinositide metabolism in the kidney have been identified, prostaglandin production and mesangial cell contraction. The regulation of prostaglandin production and its relationship to stimulated phosphoinositide metabolism are subjects of continuing study. The topic was recently reviewed by Hassid.(ABSTRACT TRUNCATED AT 400 WORDS)
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D003920:Diabetes Mellitus / Q000378:metabolism; D005920:Glomerular Mesangium / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010281:Parathyroid Hormone; D010716:Phosphatidylinositols; D010743:Phospholipids; D011453:Prostaglandins; D007294:Inositol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000251:Adenosine Triphosphatases; D002118:Calcium