Heterogeneous distribution of the conjugation activity of acetaminophen and p-nitrophenol in isolated rat liver cells.
The uneven distribution of the glucuronidation and sulfation activity of acetaminophen (APAP) and p-nitrophenol (PNP) in liver was studied using centrilobular and periportal regions of isolated rat hepatocytes obtained by Percoll density gradient centrifugation, in a manner similar to that for harmol reported previously. The glucuronidation of APAP and PNP occurred predominantly in the periportal region. Glucuronidation activity of APAP in the centrilobular region was not detected. This finding may reflect the existence of different forms of uridine diphosphate-glucuronyltransferase (UDPGT) for APAP and PNP. The regional difference in Km values was observed for PNP, but not for harmol as reported in the previous paper. This suggests the existence of multiple forms of UDPGT for PNP as well as the heterogeneous distribution of this enzyme in liver lobules. The sulfation rates of APAP and PNP in the centrilobular region were smaller than those in the periportal region. The regional difference of APAP sulfation was due to different Vmax values. As shown in the harmol experiment, the predominant distribution of sulfation activity of APAP and PNP in the periportal region agreed with the results in the perfused liver previously reported by other investigators but that of glucuronidation activity was at variance with them.
Araya
H
H
Mizuma
T
T
Horie
T
T
Hayashi
M
M
Awazu
S
S
D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D002458:Cell Fractionation; D005965:Glucuronates / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009596:Nitrophenols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism
D005965:Glucuronates; D009596:Nitrophenols; D013431:Sulfates; D000082:Acetaminophen; C001326:harmol; D006247:Harmine; C024836:4-nitrophenol