title: Thromboxane synthase inhibition: implications for prostaglandin endoperoxide metabolism. II. Testing the 'redirection hypothesis' in an acute intravenous challenge model.
abstract: In the preceding paper we described the characterisation of an acute intravenous challenge model for the evaluation of the effects of thromboxane synthase inhibition (TXSI) on eicosanoid metabolism. Herein we describe the biochemical pharmacology of two TXSI and aspirin in this model. Both TXSI caused significant inhibition of plasma TXB2 in vivo without elevation of 6-oxo-PGF1 alpha levels. Similar results were obtained when combined levels of 6-oxo-PGF1 alpha,13,14 dihydro 6-oxo-PGF1 alpha,13,14 dihydro 6,15-dioxo-PGF1 alpha and 6-oxo-PGE1 were measured as an index of PGI2 biosynthesis (PGI2m). Thus no evidence of in vivo redirection of PGH2 to PGI2 was found. Ex vivo experiments performed in serum gave an apparent stimulation of immunoreactive 6-oxo-PGF1 alpha following TXSI but RPHPLC analysis of extracted serum showed that this stimulation was accounted for by increase in a product co-eluting with [3H]PGF2 alpha. The implications of these findings in relation to TXSI and receptor antagonists are discussed.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D011449:Prostaglandin Endoperoxides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C029245:UK 34787; D013930:Thromboxane-A Synthase; D001241:Aspirin