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A novel inhibitory effect on prostacyclin synthesis of coupling factor 6 extracted from the heart of spontaneously hypertensive rats.

Authors: Osanai, T  Kamada, T  Fujiwara, N  Katoh, T  Takahashi, K  Kimura, M  Satoh, K  Magota, K  Kodama, S  Tanaka, T  Okumura, K 
Citation: Osanai T, etal., J Biol Chem. 1998 Nov 27;273(48):31778-83.
Pubmed: (View Article at PubMed) PMID:9822642

The possible presence of an unknown prostacyclin synthesis inhibitory substance has been reported in some strains of rats. We purified the inhibitory substance from the heart of spontaneously hypertensive rats by collecting active fractions after gel-filtration column chromatography and two steps of reverse-phase high performance liquid chromatography. The amino acid composition and automated gas-phase sequencing of the full-length substance and fragments cleaved by AspN indicated that the prostacyclin-inhibitory peptide was identical to coupling factor 6. Recombinant rat coupling factor 6, which was synthesized using a cleavable fusion protein strategy, attenuated base-line and bradykinin (10(-6) M)-induced prostacyclin synthesis and [3H]arachidonic acid (AA) release in human umbilical vein endothelial cells in a dose-dependent manner (10(-9)-10(-7) M). Exogenous AA- and prostaglandin H2-induced prostacyclin synthesis were unchanged even after treatment with 10(-7) M recombinant coupling factor 6. Base-line and bradykinin-induced [3H]AA release were suppressed by arachidonyltrifluoromethyl ketone, a relatively specific inhibitor of cytosolic phospholipase A2 at 40 microM, and simultaneous administration of coupling factor 6 showed no further effect. Neither oleyloxyethyl phosphorylcholine at 1 microM nor bromoenol lactone at 1 microM affected AA release. Preincubation (1 min) with 10(-7) M recombinant coupling factor 6 had no influence on adenosine diphosphate- and collagen-induced platelet aggregations. We conclude that coupling factor 6 possesses a novel function of prostacyclin synthesis inhibition in endothelial cells via suppression of Ca2+-dependent cytosolic phospholipase A2, although it is unclear whether coupling factor 6 functions in normal conditions or only in pathophysiological states.

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RGD ID: 13800919
Created: 2018-10-23
Species: All species
Last Modified: 2018-10-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.