Calcium dobesilate (Doxium) as a prostaglandin synthetase inhibitor in pregnant human myometrium in vitro

Summary This comparative study on the effect of calcium dobesilate and indomethacin on prostaglandin biosynthesis was performed on microsomal fractions of pregnant human myometrium. Both drugs inhibited prostaglandin synthesis, indomethacin being more potent. Calcium dobesilate inhibited, in a dose-dependent manner, the synthesis of 6-oxo-PGF₁, PGF₂, PGE₂ and TXB₂. Its inhibitory action is comparable to that of etamsylate.     

Etamsylate as inhibitor of prostaglandin biosynthesis in pregnant human myometrium in vitro

Summary The effects of etamsylate on prostaglandin (PG) biosynthesis in microsomes of pregnant human myometrium in vitro have been determined, and compared with those of indomethacin. Both drugs inhibited PG biosynthesis, indomethacin being the more potent inhibitor of the two. Etamsylate inhibited synthesis of 6-oxo-PGF₁, PGF₂, PGE₂, and thromboxane B₂; increasing the concentration of etamsylate increased the inhibition of synthesis. It is suggested that etamsylate has no anti-cyclo-oxygenase activity, but acts by inhibiting the activity of prostacyclin synthetase, endoperoxide reductase, endoperoxide isomerase, and thromboxane synthetase.     

Radioimmunological determination of prostaglandin D2 synthesis in human thrombocytes

Summary A specific radioimmunoassay for prostaglandin D₂ was developed. Using the radioimmunoassay, prostaglandin D₂ synthesis by human thrombocytes was measured. While the cyclooxygenase inhibitor indomethacin inhibits formation of prostaglandin D₂, increased formation of prostaglandin D₂ was observed in the presence of the thromboxane synthetase inhibitor imidazole.This work was supported by the Deutsche Forschungsgemeinschaft.     

Effects on prostaglandins F2α, I2, and indomethacin on isolated coronary arteries from healthy and alloxandiabetic dogs

Summary Contractile responses of isolated coronary arteries from healthy and alloxan-diabetic dogs to prostaglandin F₂ were enhanced by indomethacin and inhibited by prostaglandin I₂. The potentiation by indomethacin was more prominent in diabetic vessels than in normal arteries.     

A study of vasoactive intestinal polypeptide (VIP) stimulated intestinal fluid secretion in rat and its inhibition by indomethacin

4 groups of rats were studied under anaesthesia to assess the effect of VIP and the influence of the prostaglandin synthetase inhibitor indomethacin in isolated bowel loops. VIP produced a highly significant increase in the luminal fluid content and this was completely inhibited by addition of indomethacin.     

A study of vasoactive intestinal polypeptide (VIP) stimulated intestinal fluid secretion in rat and its inhibition by indomethacin

Summary 4 groups of rats were studied under anaesthesia to assess the effect of VIP and the influence of the prostaglandin synthetase inhibitor indomethacin in isolated bowel loops. VIP produced a highly significant increase in the luminal fluid content and this was completely inhibited by addition of indomethacin.     

Do prostaglandins mediate the somatostatin preventive effect on gastric lesion?

The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.     

Do prostaglandins mediate the somatostatin preventive effect on gastric lesion?

Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

Dopamine-induced relaxation in human pulmonary arteries

Dose-dependent relaxations were induced by dopamine in human pulmonary arteries that had been contracted with prostaglandin F2 alpha without alpha-adrenergic blocking agents. The dopamine-induced relaxation was inhibited by haloperidol and fluphenazine, but not by domperidone, suggesting that this relaxation was mediated via DA1 receptors.     

Inhibition of TSH-stimulated thyroid hormone release and potentiation of TRH-stimulated TSH release by indomethacin in perifusion systems of rat thyroids and pituitaries

Using indomethacin (Ind), a prostaglandin synthesis inhibitor, in vivo experiments in rats and in vitro experiments with perifusion systems of rat thyroids and pituitaries were conducted. After 35 days of intragastric infusion of Ind, serum TSH levels were markedly increased, the thyroid was swollen and, as a consequence, T3 and T4 levels were normal. The T3 release from perifused rat thyroids under continuous stimulation with 10 mU/ml TSH was inhibited significantly (p less than 0.01) by 1.0 X 10(-6) M Ind. On the other hand, the TSH release from perifused rat pituitaries under TRH stimulation was enhanced conspicuously by Ind. It was concluded that Ind decelerated thyroid hormone release from the thyroid and accelerated TSH release from the pituitary in perifusion systems.     

Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition

Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.     

Inhibition of TSH-stimulated thyroid hormone release and potentiation of TRH-stimulated TSH release by indomethacin in perifusion systems of rat thyroids and pituitaries

Summary Using indomethacin (Ind), a prostaglandin, synthesis inhibitor, in vivo experiments in rats and in vitro experiments with perifusion systems of rat thyroids and pituitaries were conducted. After 35 days of intragastric infusion of Ind, serum TSH levels were markedly increased, the thyroid was swollen and, as a consequence, T₃ and T₄ levels were normal. The T₃ release from perifused rat thyroids under continuous stimulation with 10 mU/ml TSH was inhibited significantly (p<0.01) by 1.0×10^–6 M Ind. On the other hand, the TSH release from perifused rat pituitaries under TRH stimulation was enhanced conspicuously by Ind. It was concluded that Ind decelerated thyroid hormone release from the thyroid and accelerated TSH release from the pituitary in perifusion systems.     

Endogenous pyrogen formation by human blood monocytes stimulated by polyriboinosinic acid:Polyribocytidylic acid

The pyrogenic response to supernatants from human blood monocytes stimulated with polyriboinosinic acid:polyribocytidylic acid (poly I:C) was characteristic of a response to endogenous pyrogen in that it was brief and monophasic, and was destroyed by heating the supernatants at 70°C for 30 min. Pyrogen production was unimpaired when the incubations were carried out in the presence of cycloheximide (50 g/ml; an inhibitor of protein synthesis) or indomethacin (50 g/ml; an inhibitor of prostaglandin synthesis). Also, neither interferon, interleukins, tumor necrosis factor nor prostaglandin E₂ were detectable in the supernatants from the poly I:C-stimulated human monocytes.     

Role of 5-hydroxytryptamine in prostaglandin E1-induced potentiation of hexobarbitone hypnosis in albino rats.

PGE1 potentiated, while diclofenac, a prostaglandin synthesis inhibitor, antagonized hexobarbitone hypnosis in rats. PGE1-induced potentiation of hexobarbitone sleep was inhibited by a 5HT synthesis inhibitor and by a 5HT receptor blocker, suggesting that this potentiation is 5HT mediated.     

Stimulating effect of thromboxane B2 on isolated rat atria

Summary Thromboxane B₂ enhanced the beating frequency and the contractile tension of isolated rat atria. Both effects were inhibited by propranolol, by pretreatment with 6-hydroxydopamine, or after inhibition of prostaglandins synthesis with indomethacin and acetylsalicylic acid.This work has been supported by grant 6638 from CONICET (Argentina).     

Suppression by the cyclohexanetrione Ro 31-0521 of retinoic acid-induced teratogenicity

The cyclohexanetrione Ro 31-0521, which stimulates prostaglandin synthesis, inhibited retinoic acid-induced cartilage degradation in vitro and suppressed the congenital forelimb malformations in rats treated with retinoic acid on day 13 of gestation in a dose-dependent manner.     

Stimulation of gastric secretion by prostaglandin F2 alpha in rats.

In rats with chronic gastric fistulas, prostaglandin F2 alpha stimulated the gastric acid secretion in graded doses of 50, 100, 200 and 400 microgram/kg b.wt, while higher doses above 1 mg/kg b.wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E1 could not be altered or modified by subsequent treatment of prostaglandin F2 alpha, while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.     

Decidual cell reaction in ovariectomized-adrenalectomized rats

Enhancement of decidual cell reaction (DCR) following adrenalectomy was reversed by corticosterone as well as indomethacin. The results suggest the adrenal involvement in DCR through uterine prostaglandin production.