The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2′-dibutyryladenosine-3/5′-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 μM dibutyryl-cAMP plus 1.7 (μM 16,16-dimethyl-PGE2 = 99 ± 6% of rate with 0.34 μM dibutyryl-cAMP alone; mean ± SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3′,5′-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2.

Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 μM phenylephrine + 1.7 μM 16,16-dimethyl-PGE2 = 65 ± 10% of rate with 8 μM phenylephrine alone, N = 4, P < 0.05; 4.9 μM angiotensin 11 + 1.7 μM 16,16-dimethyl-PGE2 = 75 ± 7% of rate with 4.9 μM angiotensin II alone, N = 4, P < 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 μg/mlA23187 + 1.7μM16,16-dimethyl-PGE2 = 83 ± 5% of rate with 0.55 μg/ml A23187 alone, N = 7, P < 0.05).

Thus, PGE can inhibit both cAMP-dependent and cAMP-independent hormone-stimulated glycogenolysis. The results suggest two sites of inhibition, one consistent with inhibition of adenylate cyclase stimulation and a second inhibiting calcium-mediated stimulation at an undefined site.

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