Output and effects of thromboxane produced by the liver perfused with phorbol myristate acetate.
The capacity of the perfused rat liver to produce thromboxane after stimulation by phorbol myristate acetate was examined. A total of 109 +/- 20 and 155 +/- 28 pmol/g liver were found in the perfusate and in the bile, respectively, after 40 min. The amount of thromboxane recovered in the perfusate and in the bile accounted for 12.6% of the production calculated from the same number of Kupffer cells in primary cultures, indicating that a major part of thromboxane was taken up and inactivated by hepatocytes. The effect of endogenously synthesized thromboxane on the liver was assessed by using CGS 13080, a thromboxane synthase inhibitor, or BM 13.177, a thromboxane receptor antagonist. 20 nM CGS 13080 in the perfusate inhibited the synthesis of thromboxane and at the same time the elevation of portal pressure and glycogenolysis following administration of phorbol 12-myristate 13-acetate (PMA). The thromboxane receptor antagonist BM 13.177 did not inhibit the synthesis of thromboxane, but reduced the PMA-related elevation of portal pressure and glycogenolysis to the same extent (greater than 60%) as CGS 13080. Sodium nitroprusside, a vasodilator, inhibited the rise in portal pressure caused by PMA to the same extent as CGS 13080 or BM 13.177 but reduced the increase in glycogenolysis only by 25%. These results indicate that thromboxane released by stimulated Kupffer cells of the liver elevates portal pressure and glycogenolysis in the perfused rat liver, although by different mechanisms.
Tran-Thi
T A
TA
Biochemisches Institut der Albert-Ludwigs-Universität, Freiburg i. Br.
Gyufko
K
K
Reinke
M
M
Decker
K
K
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; D011453:Prostaglandins; D011725:Pyridines; D013449:Sulfonamides; D013929:Thromboxane B2; C040624:sulotroban; C037787:pirmagrel; D013930:Thromboxane-A Synthase; D013755:Tetradecanoylphorbol Acetate