Treatment in vivo with Ph CL28A alters prostaglandin E2, prostacyclin and leukotriene C4 metabolism in rat isolated lung.
We have studied the effects of a potent inhibitor of prostaglandin (PG) catabolism, Ph CL28A, given in vivo, on PG metabolism in rat perfused lungs, isolated at different times after treatment. Two doses of Ph CL28A were used, 10 and 30 mg/kg, and lungs isolated at 1, 2 and 4h after a single injection (i.p.). The catabolism of exogenous PGE2 was decreased for up to 2h after injection. Synthesis of PGI2 using exogenous arachidonic acid, was increased by treatment with Ph CL28A. Stimulation of the turnover of endogenous arachidonic acid with the calcium ionophore A23187 led to the synthesis of LTC4 as well as PGI2. Treatment in vivo with Ph CL28A, decreased the output of LTC4 but increased that of PGI2. However in the presence of indomethacin, the perfused lung did not form any PGI2 and the output of LTC4 was still inhibited by Ph CL28A. We conclude that the inhibition of LT formation in lung by Ph CL28A was not due to the increased production of PGI2. These two properties, inhibition of LT synthesis and potentiation of PGI2 formation, may synergize in vivo to give antiinflammatory activity.
Pankhania
J J
JJ
Department of Pharmacology, Hunterian Institute, Royal College of Surgeons, Lincoln's Inn Fields, London.
Bakhle
Y S
YS
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001391:Azo Compounds / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism*
D001391:Azo Compounds; D013189:SRS-A; D016718:Arachidonic Acid; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; C047498:Ph CL 28A; D011464:Epoprostenol; D006911:Hydroxyprostaglandin Dehydrogenases; D015232:Dinoprostone