Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes.
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 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM 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 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008112:Liver Glycogen; D011458:Prostaglandins E; D000804:Angiotensin II; D010656:Phenylephrine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP; D015064:16,16-Dimethylprostaglandin E2; D004837:Epinephrine