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British Journal of Pharmacology Apr 19801 The following experiments were undertaken to confirm that prostaglandin is necessary for noradrenaline to exert its full vasoconstrictor effect in rat mesenteric blood...
1 The following experiments were undertaken to confirm that prostaglandin is necessary for noradrenaline to exert its full vasoconstrictor effect in rat mesenteric blood vessels. Prostaglandin release and inactivation were also studied. 2 The cyclo-oxygenase inhibitor, 5, 8, 11, 14-eicosatetraynoic acid caused a significant depression of the concentration-effect curve to noradrenaline. As with indomethacin, responses were restored to control levels by prostaglandin E2 (PGE2) but PGE2 did not restore responses to noradrenaline depressed by papaverine. 3 PGE2-like activity was released from tissues at rest, equivalent to 50 +/- 20 pg PGE2/min. The substance was probably a stable prostaglandin since activity remained on acidifying and extracting into chloroform. The increase in release stimulated by noradrenaline was reduced below resting values by indomethacin. 4 There was a net loss of 7 +/- 1 and 1 +/- 0.2 ng PGE2/min from tissues perfused with 40 and 4 ng/min PGE2 respectively. No uptake occurred at lower PGE2 perfusion rates. 5 When indomethacin was used to depress responses to noradrenaline 15(S)-15-methyl PGE2 methyl ester was 12 times more potent than PGE2 in restoring responses to control values. The cyclic endoperoxide analogue U-46619 caused only partial restoration of indomethacin-depressed responses to noradrenaline but increased perfusion pressure at 2 ng/ml and above. 6 The results confirm that endogenous prostaglandin release, possible of PGE2, is obligatory to the full vasoconstrictor effect of noradrenaline. Noradrenaline increases the amount of prostaglandin released which may be taken up and inactivated by 15-hydroxy prostaglandin dehydrogenase or beta-oxidase. U-46619 may mimic both PGE2 and thromboxane A2.
Topics: 5,8,11,14-Eicosatetraynoic Acid; Animals; Blood Vessels; In Vitro Techniques; Indomethacin; Mesentery; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Prostaglandins E; Rats; Vasoconstrictor Agents
PubMed: 7378646
DOI: 10.1111/j.1476-5381.1980.tb10869.x -
British Journal of Pharmacology May 19831 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney.... (Comparative Study)
Comparative Study
1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of authentic 6-keto PGE1. 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. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 6-keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea-pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. 6 Rutin (50 microM) potently inhibited synthesis of 6-keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.
Topics: Alprostadil; Animals; Epoprostenol; Guinea Pigs; In Vitro Techniques; Kidney; Male; Prostaglandins E; Rabbits; Rats; Rats, Inbred Strains; Species Specificity; Time Factors
PubMed: 6347300
DOI: 10.1111/j.1476-5381.1983.tb10507.x -
Zhongguo Yao Li Xue Bao = Acta... Sep 1986
Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Edema; Female; Granuloma; Male; Mice; Prostaglandins E; Rats
PubMed: 2954414
DOI: No ID Found -
FEBS Letters Apr 1984The effect of E-series prostaglandins (PGE) on hepatic glucose metabolism is controversial. This study uses isolated rat hepatocytes and exogenously added PGE analogs or...
The effect of E-series prostaglandins (PGE) on hepatic glucose metabolism is controversial. This study uses isolated rat hepatocytes and exogenously added PGE analogs or frequent native PGE additions (to compensate for hepatic PGE degradation) to define PGE's effect on hepatic glycogenolysis. 16,16-Dimethyl PGE2, 15(S),15-methyl PGE2, PGE1 and PGE2 all inhibit glucagon-stimulated glycogenolysis. It is concluded that E-series prostaglandins can act directly on the liver to inhibit glycogenolysis.
Topics: Alprostadil; Animals; Dinoprostone; Glucagon; Liver; Liver Glycogen; Male; Perfusion; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains
PubMed: 6585308
DOI: 10.1016/0014-5793(84)80336-1 -
British Medical Journal Sep 1978
Topics: Humans; Male; Phenytoin; Prostaglandins E; Receptors, Muscarinic; Urethra; Urinary Bladder
PubMed: 568015
DOI: 10.1136/bmj.2.6138.704-c -
British Journal of Pharmacology Sep 19771 The effects of intravenous prostaglandin E1 and endotoxin were studied in young chickens (11-17 days old). 2 At a thermoneutral ambient temperature (31 degrees C),...
1 The effects of intravenous prostaglandin E1 and endotoxin were studied in young chickens (11-17 days old). 2 At a thermoneutral ambient temperature (31 degrees C), intravenous prostaglandin E1, produced behavioural and electrocortical sleep, increased oxygen consumption and, after an initial fall, elevated body temperature. Below thermoneutrality (16 degrees C), the initial hypothermic effect was more marked and oxygen consumption was lowered. 3 The soporific actions of prostaglandin E1 were sufficient to counteract dexamphetamine-induced behavioural and electrocortical arousal and vocalization. 4 Intravenous injection of the O-somatic antigen of Shigella dysenteriae evoked, after a latent period, long lasting hyperthermia. This indicates that in young chicks the blood brain barrier is probably permeable to endotoxins.
Topics: Animals; Behavior, Animal; Body Temperature; Chickens; Electroencephalography; Endotoxins; Female; Hypothalamus; Injections; Oxygen Consumption; Prostaglandins E; Shigella dysenteriae; Time Factors; Vocalization, Animal
PubMed: 334307
DOI: 10.1111/j.1476-5381.1977.tb09736.x -
Kidney International Jun 1988The onset of infection is associated with increases in renal blood flow and sodium excretion. Our studies provide evidence that the natriuresis is mediated by...
The onset of infection is associated with increases in renal blood flow and sodium excretion. Our studies provide evidence that the natriuresis is mediated by stimulation of renal prostaglandin production by the cytokine, interleukin-1. A dose-dependent natriuresis and diuresis was elicited in conscious rats with bolus intravenous injections of human recombinant interleukin-1-beta (hrIL-1). Injection of 1.5, 3 and 24 micrograms hrIL-1 increased sodium excretion by 2.4 +/- 0.9 microEq/min, 4.0 +/- 0.8 microEq/min and 5.4 +/- 0.3 microEq/min, respectively. The natriuresis was preceded by a corresponding increase in urinary PGE excretion (80%, 110% and 296%, respectively). The natriuresis elicited by 3 micrograms hrIL-1 was independent of changes in glomerular filtration rate or effective renal plasma flow. IL-1 induced an increase in rectal temperature, (0.6 +/- 0.2 degrees C) and a modest increase in mean arterial pressure (12 +/- 3 mm Hg) within 10 minutes of injection. However, during the period of maximal natriuresis (40 to 100 min), blood pressure and rectal temperature were not significantly different from control. Pretreatment with the cyclooxygenase inhibitor, ibuprofen, significantly attenuated the natriuretic response and indomethacin completely abolished the natriuresis. These results identify IL-1 as a factor which stimulates renal PGE synthesis, and increases sodium excretion, independent of changes in glomerular filtration rate. We propose that IL-1-induced natriuresis may be a component of the overall acute phase response which is actively mounted by the host during infection.
Topics: Animals; Consciousness; Cyclooxygenase Inhibitors; Humans; Interleukin-1; Kidney; Male; Natriuresis; Prostaglandins E; Rats; Rats, Inbred Strains; Recombinant Proteins
PubMed: 3136271
DOI: 10.1038/ki.1988.111 -
The Journal of Biological Chemistry Aug 1982Bradykinin stimulates protein production as well as prostaglandin production by lung fibroblasts in culture. When prostaglandin (PG) synthesis by the fibroblasts is...
Bradykinin stimulates protein production as well as prostaglandin production by lung fibroblasts in culture. When prostaglandin (PG) synthesis by the fibroblasts is inhibited with indomethacin, then bradykinin also stimulates collagen production. In the presence of indomethacin, the increase in protein production by bradykinin is much higher than in its absence. The addition of exogenous PGE2 to the fibroblasts which have been treated with indomethacin inhibited the stimulating effect of bradykinin on total protein production, especially collagen production. The concentration of PGE2 added was in the range of that produced by the fibroblasts. The degree of inhibition by PGE2 was dependent on the concentration of PGE2 added to the cultures. These results point out an interaction between bradykinin and PGE2 in the regulation of protein production by fibroblasts with PGE2 acting as a feedback mechanism to dampen the effect of bradykinin.
Topics: Bradykinin; Collagen; Dinoprostone; Drug Synergism; Female; Fibroblasts; Humans; Indomethacin; Lung; Pregnancy; Prostaglandins E; Protein Biosynthesis
PubMed: 6954152
DOI: No ID Found -
Postgraduate Medical Journal Apr 1981A case of uterine rupture following extra-amniotic prostaglandin E2 with a subsequent obstetrical complication is reported.
A case of uterine rupture following extra-amniotic prostaglandin E2 with a subsequent obstetrical complication is reported.
Topics: Abortion, Therapeutic; Adolescent; Female; Humans; Pregnancy; Prostaglandins E; Uterine Rupture
PubMed: 7291112
DOI: 10.1136/pgmj.57.666.265 -
The Journal of Investigative Dermatology Feb 1986Since the biochemical events leading to cutaneous inflammation in atopic dermatitis and psoriasis are unknown, we studied the levels of arachidonic acid-derived...
Since the biochemical events leading to cutaneous inflammation in atopic dermatitis and psoriasis are unknown, we studied the levels of arachidonic acid-derived mediators of inflammation as well as histamine in the suction blister fluid obtained from lesional and nonlesional skin of patients with these dermatoses. Mediator levels were determined radioimmunologically. Skin from healthy controls and uninvolved skin from patients contained very low or unmeasurable levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene (LT) B4. In contrast, higher levels of LTB4-like immunoreactivity were detected in suction blister fluid from lesional atopic dermatitis skin, and even higher concentrations occurred in psoriasis lesions. LTB4-like immunoreactivity from atopic dermatitis suction blister fluid cochromatographed on reverse-phase high-pressure liquid chromatography with authentic LTB4, thus excluding cross-reaction of the LTB4-antibody with arachidonic acid or monohydroxyeicosatetraenoic acids. In contrast, suction blister concentrations of the cyclooxygenase metabolite of arachidonic acid prostaglandin (PG) E2 showed no significant differences between lesional and nonlesional patient skin and healthy control skin. PGD2 determined as a stable metabolite could not be detected in these samples. Histamine concentrations in lesional skin were within normal range. The elevated levels of the potent proinflammatory and immunomodulating mediator LTB4 could be involved in the pathogenesis of cutaneous inflammation in atopic dermatitis and psoriasis. In addition, they might explain the therapeutic efficiency of glucocorticosteroids, which among other actions inhibit the release of arachidonic acid from phospholipid stores by blocking the enzyme phospholipase A2. However, the specificity of disease expression in atopic dermatitis and psoriasis must be due to factors other than cutaneous LTB4 elevation.
Topics: Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Dermatitis, Atopic; Dinoprostone; Female; Histamine; Humans; Leukotriene B4; Male; Middle Aged; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Psoriasis; Skin
PubMed: 3018086
DOI: 10.1111/1523-1747.ep12284061