Effects of dexamethasone on cyclic nucleotide accumulation in glomeruli

H. E. Abboud, S. V. Shah, T. P. Dousa

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Abstract

Cyclic nucleotides were shown to modulate inflammatory processes in a variety of tissues. In previous studies the authors found that local mediators of inflammation stimulate cyclic nucleotide generation in glomeruli. In the present experiments the authors examined whether treatment with high doses of glucocorticoid dexamethasone would modulate levels of cAMP and cGMP in glomeruli or its response to mediators of inflammation. Glomeruli and tubules were isolated from control rats and rats treated for 3 days with 2 mg of dexamethasone intraperitoneally per day. Basal levels (without added hormonal agents) of cAMP and cGMP in glomeruli and tubules were not different in control and dexamethasone-treated rats. On the other hand, the extent of cAMP increase in glomeruli in response to histamine (10-4M) and to serotonin (10-4M) in dexamethasone-treated rats was significantly (p<0.025) lower than in controls. The extent of cAMP elevation in cortical tubules in response to PTH was not different between dexamethasone-treated and control animals. Histamine (10-4M) and carbamylcholine (10-4M) increased cGMP in dexamethasone-treated glomeruli to a significantly (p<0.025) lesser extent than in placebo-treated controls, but the increment in cGMP in response to 10-3M nitroprusside in glomeruli was not significantly different in controls and dexamethasone-treated rats. Present results show that treatment with a pharmacologic dose of dexamethasone does not alter basal accumulation of cAMP and cGMP in glomeruli, but significantly blunts sensitivity of the cyclic nucleotide system to stimulatory effects of histamine, serotonin, and carbamylcholine. The observed changes in glomerular cGMP and cAMP systems may relate to pharmacologic effects of dexamethasone on glomerular filtration and to the therapeutic action of glucocorticoids in the treatment of glomerular diseases, i.e., those caused by immune-inflammatory injury.

Original languageEnglish (US)
Pages (from-to)708-717
Number of pages10
JournalJournal of Laboratory and Clinical Medicine
Volume94
Issue number5
StatePublished - Dec 1 1979

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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