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Effect of nonsteroidal anti‐inflammatory drugs on glycogenolysis in isolated hepatocytes
Author(s) -
Brass Eric P.,
Garrity Maureen J.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08919.x
Subject(s) - glycogenolysis , glucagon , endocrinology , chemistry , medicine , ibuprofen , stimulation , cyclooxygenase , hepatocyte , piroxicam , prostaglandin e , prostaglandin e2 , pharmacology , glycogen , hormone , biochemistry , enzyme , biology , in vitro , alternative medicine , pathology
1 E‐series prostaglandins have previously been demonstrated to inhibit hormone‐stimulated glycogenolysis when added to isolated hepatocytes of the rat. In the present study, the effect of nonsteroidal anti‐inflammatory drugs, which inhibit cyclo‐oxygenase activity, on glycogenolysis was examined in the hepatocyte model. Ibuprofen (80 μM), indomethacin (50 μM) and meclofenamate (60 μM) all increased rates of glycogenolysis when added under basal conditions. In contrast, piroxicam (50 μM) had no effect on glycogenolysis in the hepatocyte system. Concentrations of ibuprofen below 80 μM did not significantly increase rates of glycogenolysis. 2 Ibuprofen (80 μM) had no effect on glycogenolysis in the presence of 10 −5 M adrenaline or 5 × 10 −7 M glucagon, but did increase glycogenolytic rates in the presence of 5 × 10 −8 M glucagon. 3 Ibuprofen‐stimulated glycogenolysis was inhibited by addition of prostaglandin E 2 (PGE 2 ). Under conditions where glucagon‐stimulated glycogenolysis was inhibited by exogenous PGE 2 , addition of ibuprofen (80 μM) increased the rate of glycogenolysis. 4 Ibuprofen had no effect on basal or glucagon‐stimulated hepatocyte adenylate cyclase activity. 5 In conclusion, these results demonstrate that nonsteroidal anti‐inflammatory drugs which are carboxylic acids can increase the rate of glycogenolysis in isolated hepatocytes. The high concentrations of drug required to stimulate glycogenolysis, the lack of effect of piroxicam, and the demonstration of stimulation by ibuprofen in the presence of exogenous PGE 2 all suggest that the stimulation of glycogenolysis by ibuprofen, indomethacin and meclofenamate is independent of cyclo‐oxygenase inhibition. These observations are consistent with reports that carboxylic acid nonsteroidal anti‐inflammatory drugs can interfere with hepatic intracellular calcium handling.