Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the original studies of Patak et al. in 1975 revealed that the antihypertensive and natriuretic effects of furosemide were markedly blunted or abrogated by indomethacin in both normotensive and hypertensive man, it has been postulated that the ameliorative effects of furosemide in human essential hypertension might be mediated by release of intrarenal prostaglandins. To study the direct effects of furosemide on prostaglandin biosynthesis and release, slices of rabbit renal medulla were incubated in Krebs-Ringer bicarbonate buffer, glucose 10 mM, 1-14C-arachidonic acid (AA) 10 microM, HSA /g/100 ml, 30 min 37 degrees C. Measurements were made of radioactive AA leads to PGE2, and total endogenous immunoreactive PGE2 production (iPGE2) with and without the addition of furosemide (10 microgram/ml) to the media. In the absence of furosemide AA leads to PGE2 was 73 +/- 22 nmol/30 min/g and in the presence of furosemide it fell to 30 +/- 4 nmol/30min/g. iPGE2 was 33 +/- / ng/30 min/mg and decreased to 25 +/- 3 mg with furosemide. These results indicate that the natriuresis and antihypertensive effect of furosemide in vivo, which is associated with a significant increase in urinary PGE2, is not the result of a direct stimulation of furosemide on prostaglandin synthesis but may result from a decrease in PGE metabolism, conversion to another biologically active prostaglandin or possibly be a reflection of events secondary to a direct effect of furosemide on renal hemodynamics and electrolyte excretion.
 ...
PMID:Antihypertensive effect of volume depletion: interrelation with renal prostaglandins. 69 6

Isolated cultures of mononuclear phagocytes from 12 humans (7 normal controls and 5 with cancer) produced prostaglandins (PGs) of the E series when stimulated with artificial immune complexes (HSA and anti-HSA). The amount of PGs produced by monocytes from breast cancer patients and macrophages from ascites fluid taken from patients with abdominal cancers was 4 fold that produced by blood monocytes from normal controls. Immune complex (IC) determinations from the serums of these humans (Raji cell method) showed that only patients in the advanced stages of the diseases, and none of the controls, had elevated levels of IC. In the presence of IC, there was noted a depression in the immune reactivity of mononuclear cell cultures, as determined by 3H thymidine uptake following stimulation with PHA, Con A and PWM. The depressed blastogenic response was not in all instances fully reversed by the addition of indomethacin or aspirin, indicating that PGs were not the only causative factor. It is concluded that mononuclear phagocytes elaborate immunosuppressive factors in response to stimulation by imune complexes. One of these factors is PGE. Further, this results in a homeostatic regulation which prevents damage from IC deposition and may be, in part, responsible for imunosuppression of cancer patients.
 ...
PMID:Immune-complex induced prostaglandin production by monocytes of normal human subjects and cancer patients. 740 34

We disclose herein our preliminary SAR study on the identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists. A potent EP(4) antagonist 6a (K(i)=1.4nM with 10% HSA) was identified. Furthermore, we found that an acidic group was not essential for the EP(4) antagonizing activity in the series and neutral replacements were identified. This opens a new direction for future EP(4) antagonist design.
 ...
PMID:The identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists: From acid to non-acid. 2120 3