Disease relevance of C05962

• In six additional anesthetized dogs in which the carotid arteries were ligated in order to minimize baroreflexes, intracoronary injection of 6-keto-PGE1 and PGI2 (in doses of 7, 14 and 23 micrograms) caused systemic hypotension and bradycardia [1].
• The tachycardia to the highest doses was compared to that induced by infusion of nitroprusside (500 micrograms/min i.v.). 6-keto-PGE1 and PGI2 caused significantly less baroreflex tachycardia per millimeter of mercury decrease in arterial pressure than did nitroprusside [1].
• 6-Keto-prostaglandin E1-stimulated bone resorption in organ culture [2].
• These results indicate that 6-keto-PGE1 is similar to PGI2 in that it produces maternal cotyledonary vasoconstriction, hypotension, and vasodilation in other organs [3].
• The inhibitory effect of 6-keto-prostaglandin E1 (pGE1) on the growth and survival of ascitic hepatoma (AH-130) cells in vivo was compared with currently used chemotherapeutic agents [4].

High impact information on C05962

• Either PGI2 or its inactive hydrolysis product, 6-keto-PGF1 alpha, can be enzymically transformed via the 9-hydroxyprostaglandin dehydrogenase pathway to 6-keto-PGE1 [5].
• Using platelet antiaggregatory activity as an index of stability, we found that PGI2 was largely inactivated within 10 minutes under the conditions used for incubating the slices (pH 7.4, 37 degrees C), while 6-keto-PGE1 was stable [6].
• PGE2, PGE1, PGD2 and 6-keto-PGE1 each evoked a concentration-dependent inhibition of the leukotriene formation with IC50 values of 0.07 microM, 0.18 microM, 0.27 microM and 6 microM respectively [7].
• HPLC fractions containing i-6-keto-PGE1, and coeluting with 6-keto-PGE1 standard, exhibited potent inhibition of platelet aggregation [8].
• These studies were performed to examine the effects of 6-keto-prostaglandin E1 (6-keto-PGE1) on coronary artery blood flow and reflex cardiovascular regulation [1].

Biological context of C05962

• 6-Keto-PGE1 reversed the hypertensive effects of ADP in the pulmonary vascular bed suggesting this agent may inhibit ADP-induced platelet aggregation in small intrapulmonary vessels [9].
• Effects of 6-keto-prostaglandin E1 on perinatal pulmonary vascular resistance [10].
• Prostacyclin (PGI2) is metabolized to 6-keto-prostaglandin E1 (6-keto-PGE1) which is more stable yet equipotent to PGI2 in lowering systemic arterial blood pressure in the dog [11].
• We conclude that 6-keto-PGE1 can be inactivated by enzymes with wide tissue distribution, but further studies are needed for identification of these novel enzymes and the products formed as well as to assess their significance in the intact animal [12].
• The relative potencies of PGI2, 6-keto-PGE1 and 6-keto-PGF1 alpha on renin secretion rate (RSR) and renal blood flow (RBF) were assessed in nonfiltering, beta adrenoreceptor blocked kidneys of seven anesthetized dogs [13].

Anatomical context of C05962

• Decreases in systemic arterial pressure and systemic vascular resistance were similar when 6-keto-PGE1 was injected into the right or left atrium, suggesting that the substance is not converted to less active metabolites in passage through the feline pulmonary vascular bed [9].
• At the level of platelet membranes, 6-keto-PGE1 interacts with the binding sites labelled by PGI2 [14].
• However, in platelets as well as in mesenteric artery myocytes, 6-keto-PGE1 interacts with only one class of sites as demonstrated either by binding or by adenylate cyclase studies, whereas PGI2 in the same conditions recognizes two different classes [14].
• Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1 [15].
• In five sheep a fetal intravenous infusion of 18 micrograms/min of 6-keto-PGE1 decreased mean fetal blood pressure from 43 +/- 2 to 29 +/- 2 mm Hg [3].

Associations of C05962 with other chemical compounds

• In addition to this basic mechanism PGE2 and 6-keto-PGE1 abrogate the FMLP-induced response by occupation of formyl peptide receptor of PMNs [16].
• Enzymatic inactivation of 6-keto-prostaglandin E1 in vitro: comparison with prostaglandin E1 [12].
• Treatment of intact human platelets with the tumour-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), specifically inhibited PGD2-induced cyclic AMP formation without affecting the regulation of cyclic AMP metabolism by PGI2, PGE1, 6-keto-PGE1, adenosine or adrenaline [17].
• The potency of that inhibition by either PGD2 or PGE1 was the same when zymosan was used as a stimulator whereas PGE2 and 6-keto-PGE1 were by 13 and 21 times less potent inhibitors of O2-) in zymosan-stimulated as compared to FMLP-activated PMNs [16].
• The effects of 6-keto-PGE1 on vascular resistance and vascular responses to sympathetic nerve stimulation and vasoconstrictor hormones were investigated in the feline mesenteric vascular bed [18].

Gene context of C05962

• 6-Keto-prostaglandin E1 is more potent than prostaglandin I2 as a renal vasodilator and renin secretagogue [13].
• Single-blind study of epoprostenol and 6-keto-prostaglandin E1 in man: effects of platelet aggregation and plasma renin [19].
• ANP, either infused in vivo immediately before sacrifice or added to the incubation tubes, stimulated the synthesis of PGE2 and 6-keto-PGE1 alpha by isolated rat glomeruli but not by medullary or papillary slices [20].
• The effects of 6-keto-PGE1 on aggregatory responses to arachidonic acid (AA), adenosine diphosphate (ADP) and collagen were studied in human platelet-rich plasma (PRP) [21].
• The effect of 6-keto-prostaglandin E1 on human lymphocyte cAMP levels [22].

Analytical, diagnostic and therapeutic context of C05962

• Hypotensive response to prostacyclin and 6-keto-PGE1 following hepatectomy in the rat [11].
• Prosthesis/tissue complexes explanted after 2 weeks to 9 months were studied grossly, photographed, sectioned for light microscopy and scanning and transmission electron microscopy, and assayed for 6-keto-PGE1 alpha contents in inner capsular tissues [23].
• Either intra-aortic or intravenous injections of a stable prostaglandin metabolite, 6-keto-prostaglandin E1 (6-keto-PGE1), caused similar dose-dependent falls in blood pressure and reductions in renovascular resistance in the anesthetized rat [24].
• 6-Keto-PGE1, was 3.0 and 2.5 times more potent on the two bioassay tissues, respectively, but approximately 3 times less so as inhibitor of platelet aggregation [25].
• A direct comparison of the relative potencies of the prostaglandins PGI2 and 6-keto-PGE1 to induce renin release was made in the isolated rat kidney, which was perfused with a synthetic medium at constant perfusion pressure [26].

References