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Effects of indomethacin on renomedullary interstitial cells
Abstract:
The effects of indomethacin, an inhibitor of prostaglandin synthesis, on rat renomedullary interstitial cells were studied. Indomethacin, 5 mg. per kg. intravenously in divided doses over 48 hours, resulted in reduced granularity of interstitial cells (5.56+/-1.37 versus 9.85+/-1.07 granules per cell, (p is less than 0.001) and, at the same time, inhibited the incorporation of 14C-arachidonate into renomedullary phospholipids (715 + 11 versus 1299 + 42 c.pm.per mug. of lipid orthophosphate; p is less than 0.001) 14C-arachidonate incorporation into cortical phospholipids was not affected by indomethacin. There was a close correlation between individual granule counts and 14C-arachidonate incorporation into medullary phospholipids for both control (r=0.85) and indomethacin-treated animals (r=0.9). Radioactivity in the cytosol fraction was depressed by indomethacin reflecting inhibition of prostaglandin synthesis; cytosol radioactivity correlated closely with individual granule count (r=0.81) in the indomethacin-treated but not in the control rats. Indomethacin given as a single dose 4 hours prior to sacrifice resulted in a significant depression of 14C-arachidonate incorporation but did not affect granularity of interstitial cells. The results suggest that granularity of renomedullary interstitial cells reflects the activity of prostaglandin synthesis and the rate of prostaglandin precursor delivery from microsomal phospholipids.
Insights
Indomethacin treatment reduced granularity in rat renomedullary interstitial cells and inhibited prostaglandin synthesis. This suggests cell granularity reflects prostaglandin production and precursor delivery.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Prostaglandins play a crucial role in renal function.
- Renomedullary interstitial cells are involved in prostaglandin synthesis.
- The morphological changes in these cells related to prostaglandin synthesis are not fully understood.
Purpose of the Study:
- To investigate the effect of indomethacin, a prostaglandin synthesis inhibitor, on rat renomedullary interstitial cells.
- To determine if the granularity of these cells correlates with prostaglandin synthesis activity.
Main Methods:
- Rats were treated with indomethacin (5 mg/kg IV over 48 hours) or a single dose 4 hours prior to sacrifice.
- Granularity of renomedullary interstitial cells was quantified.
- Incorporation of 14C-arachidonate into renomedullary and cortical phospholipids was measured.
- Radioactivity in the cytosol fraction was assessed.
Main Results:
- Indomethacin treatment significantly reduced interstitial cell granularity and 14C-arachidonate incorporation into renomedullary phospholipids.
- No significant effect of indomethacin was observed on 14C-arachidonate incorporation into cortical phospholipids.
- A strong positive correlation was found between interstitial cell granule count and medullary phospholipid 14C-arachidonate incorporation.
- Indomethacin reduced cytosol radioactivity, correlating with granule count in treated rats.
Conclusions:
- The granularity of renomedullary interstitial cells is a morphological indicator of prostaglandin synthesis activity.
- Indomethacin's effects suggest a link between prostaglandin precursor delivery, synthesis, and interstitial cell morphology.
- These findings provide insights into the cellular mechanisms of prostaglandin regulation in the renal medulla.