Inositol phospholipid metabolism in the kidney

D. A. Troyer, D. W. Schwertz, J. I. Kreisberg, M. A. Venkatachalam

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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 of 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. It is not clear that stimulated phosphoinositide metabolism is a necessary event for prostaglandin metabolism, but it is certainly permissive, possibly by mobilizing calcium for phospholipase A2 action. Other topics for study include diabetes-induced alterations in renal phosphoinositide metabolism. The finding of diminished glomerular inositol levels in streptozotocin diabetic rats should provide a stimulus for further in vitro and in vivo studies of phosphoinositide metabolism in diabetes. Altered phosphoinositide metabolism may, in conjunction with other features of diabetes, lead to cellular abnormalities that contribute to the renal pathology of diabetes. The possible implications for cellular regulation by phospholipid-dependent protein kinase C in the kidney have received little attention to date. It has recently been suggested that protein kinase C may be involved in the action of vasopressin on the toad urinary bladder. In summary, numerous areas of phosphoinositide metabolism in the kidney deserve further study. The filtration and transport functions of the kidney make this a particulary interesting organ since a variety of hormones modulate these activities. We hope this review will stimulate interest in the area.

Original languageEnglish (US)
Pages (from-to)51-71
Number of pages21
JournalAnnual Review of Physiology
VolumeVOL. 48
StatePublished - Jan 1 1986

ASJC Scopus subject areas

  • Physiology

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