RHC 80267 inhibits thyrotropin-stimulated prostaglandin release from rat thyroid lobes.
In the present report, we studied the effect of the diglyceride (DG) lipase inhibitor, RHC 80267 on basal and thyrotropin (TSH)-stimulated prostaglandin (PG) release from rat thyroid lobes Further, we tested the effect of RHC 80267 on phosphatidylinositol phospholipase C (PIPLC), DG lipase, and arachidonate cyclo-oxygenase activities in rat thyroid cytosol, plasma membrane, and whole homogenate preparations, respectively. Whereas RHC 80267 inhibited DG lipase activity in a dose-related manner from 0.5-10 microns (17-80% inhibition), it failed to inhibit either PIPLC or arachidonate cyclo-oxygenase activities by more than 9% when tested at 5 and 10 microns (n = 3). RHC 80267 reduced TSH-stimulated 6-keto-PGF1alpha and PGF2alpha release by 100 +/- 14% and 57 +/- 12%, respectively (means + S.E.; p less than 0.01 for both; n = 10-12); the diglyceride lipase inhibitor did not reduce basal release of either PG. These data provide additional evidence which implicate a PIPLC-DG lipase pathway in TSH-stimulated PG synthesis in thyroid.
D000818:Animals; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D003510:Cyclohexanes; D003512:Cyclohexanones; D004075:Diglycerides; D010716:Phosphatidylinositols; D011453:Prostaglandins; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D013972:Thyrotropin; D011451:Prostaglandin-Endoperoxide Synthases; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases