Cyclic AMP-dependent phosphorylation in the control of biotransformation in the liver.
The possibility of a short-term cAMP-dependent regulation of mixed-function oxidation and of glucuronide formation was investigated in isolated mouse hepatocytes and in mouse liver microsomal membranes. N6, O2-dibutyryl cAMP (in accordance with its increasing effect on gluconeogenesis) decreased aminopyrine oxidation and p-nitrophenol conjugation in isolated hepatocytes, while the phenolphthalein conjugation remained unaltered. Similar to dibutyryl cAMP the Ca2+ ionophore A 23187 also decreased aminopyrine oxidation. In cell-free systems the phosphorylation of isolated microsomal membranes by the exogenous cAMP-dependent protein kinase was inhibitory on aminopyrine oxidation and p-nitrophenol glucuronide formation but aniline oxidation and phenolphthalein glucuronidation were not affected. The correlation between the negative cAMP-dependent control of certain processes of biotransformation and the positive cAMP-dependent regulation of gluconeogenesis is discussed.
Bánhegyi
G
G
1st Institute of Biochemistry, Semmelweis University, Medical School, Budapest, Hungary.
Garzó
T
T
Mészáros
G
G
Faragó
A
A
Antoni
F
F
Mandl
J
J
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology; D005943:Gluconeogenesis; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D051379:Mice; D009596:Nitrophenols / Q000378:metabolism; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*
D005965:Glucuronates; D009596:Nitrophenols; D010635:Phenolphthaleins; C049288:p-nitrophenol glucuronide; D000632:Aminopyrine; D000001:Calcimycin; D003994:Bucladesine; D020113:Phenolphthalein; D005688:Galactosamine; D000242:Cyclic AMP; D011494:Protein Kinases