Characterization of glucose-6-phosphatase in hepatocytes. Effects of amiloride and pentamidine.
The hepatic microsomal glucose-6-phosphatase enzyme is situated inside the lumen of the endoplasmic reticulum and, for normal enzyme activity in vivo, three transport systems are needed for the substrate glucose-6-phosphate and the products phosphate and glucose. Previous studies using isolated microsomes showed that the drugs amiloride and pentamidine do not affect the glucose-6-phosphatase enzyme but can activate the glucose-6-phosphate transport system. Here we demonstrate that, very surprisingly, the addition of pentamidine (and to a lesser extent amiloride) to isolated hepatocytes results in an inhibition of the catalytic subunit of glucose-6-phosphatase.
Grant
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A
Department of Obstetrics and Gynaecology, Ninewells Hospital and Medical School, University of Dundee, U.K.
Macgregor
A M
AM
Burchell
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A
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010419:Pentamidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; D010419:Pentamidine; D000584:Amiloride; D005952:Glucose-6-Phosphatase