PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Prostanoic Acids”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1984

Influence of 'cytoprotective' drugs (carbenoxolone, zolimidine, prostanoic acid) on mucus secretion in patients with gastric ulcer.

We have studied gastric mucus secretion after carbenoxolone, zolimidine and prostanoic acid short term treatment (28 days) in patients with endoscopically demonstrated peptic gastric ulcer of the lesser curvature. Six patients were treated with carbenoxolone (300 mg/day), 6 with zolimidine (1200 mg/day) and 6 with prostanoic acid (2 g/day). All of them were submitted to gastric juice collection, before and after treatment, during 1 h at fast. On the samples of gastric juice, taken at 15 min intervals, the protein component (PC), glucosamine (GL), fucose (FU), the free N-acetyl-neuraminic acid (NANA) and sulphate groups (SG), were determined by biochemical methods. We have observed a significant increase of PC after zolimidine (P less than 0.02) and prostanoic acid (P less than 0.05) treatment, without significant variations of the other mucus components. No significant variations of mucus secretion after carbenoxolone treatment. If we compare the three drugs, we can see a significant increase of PC after zolimidine (P less than 0.005) and after prostanoic acid (P less than 0.001), compared with the results obtained after carbenoxolone. There are no significant variations of basal and stimulated (pentagastrin 6 mcg/Kg i.v.) secretory volume and acid output before and after treatment in the three groups of patients.

Adult↗
PubMed1988

Mass spectrometric identification of urinary and plasma metabolites of 9-hydroxy-19,20-bis-nor-prostanoic acid (rosaprostol).

9-Hydroxy-19,20-bis-nor-prostanoic acid (Rosaprostol) is an antiulcer compound with antisecretory and cytoprotective action. We studied the metabolites of Rosaprostol found in human plasma and in human and rat urine. Sixteen different metabolites were tentatively identified on the basis of their mass spectra. Two presumed metabolites were synthesized. To clarify the identities of some of them, deuterated Rosaprostol was administered to rats and mass spectra of the deuterated and protonated metabolites were examined. Rosaprostol is metabolized following three metabolic pathways leading, combined, to oxidized compounds with a lower number of carbons than the parent drug.

Animals↗
PubMed1982

Gastric antisecretory, antiulcer and cytoprotective properties of 9-hydroxy-19,20-bis-nor-prostanoic acid in experimental animals.

9-Hydroxy-19,20-bis-nor-prostanoic acid (IBI-C83) was evaluated on gastric acid secretion and gastric lesions induced in laboratory animals by a variety of experimental conditions: compound IBI-C83 is proved effective in decreasing basal, histamine- and pentagastrin-stimulated total acid output in rats and in pentagastrin perfused dogs. The concentration of N-acetylneuraminic acid in the gastric fluid, a marker of mucus secretion, is enhanced in rats by IBI-C83. This drug prevents gastric damage induced by non-steroidal antiinflammatory compounds such as acetylsalicylic acid, indometacin and phenylbutazone, gastric ulcers following pylorus ligation, and facilitates healing of the gastric ulcers evoked by subserosal injection of acetic acid. A prominent feature of IBI-C83 is its capacity to protect the rat from gastric damage elicited by necrotizing agents such as absolute ethanol, hydrochloric acid and hypertonic saline. This property, called "cytoprotection" and common to naturally occuring prostaglandins, is independent on the antisecretory activity of IBI-C83 and is not shared, at least in the reported experimental models, by the H2-receptor antagonist cimetidine. In spite of the prostaglandin-like properties displayed in its cytoprotective activity, compound IBI-C83 does not affect cardiovascular functions, gastrointestinal transit and uterine motility.

Animals↗
PubMed1979

Some biological activities of a series of 9a-homo-9,11-epoxy prostanoic acid analogues.

A number of stereochemical variants at C-8, C-12 and C-15 of 9a-homo-9,11-epoxy prostaglandins (PGs) have been examined for in vivo activity on blood pressure, bronchial resistance, tracheal segment pressure, heart rate and on intestinal and uterine contractility in artificially respired anaesthetised guinea-pigs; and on blood pressure and blood platelet aggregation in rats (using the extra-corporeal filter-aorta loop technique). In vitro tests for smooth muscle activity were carried out on the isolated rat fundus strip, the guinea-pig tracheal chain and the rat uterus. The following was found: 1. In the guinea-pig, in vivo, all the homo-epoxy PGs were vasopressor and bronchoconstrictor following bolus injections of 250 micrograms i.v. The effects on heart rate, and intestinal and uterine contractility were equivocal. The configurations at the chiral centres, C-8, C-12 and C-15 play an important role in determining potency. The 15-(S)-hydroxy derivatives were the most potent in stimulating vascular and respiratory muscle. The 8-iso configuration appeared to enhance potency amongst the 15-(S)-hydroxy compounds. The 15-(R)-hydroxy configuration markedly reduced constrictor potency. The same pattern of activity was seen on rat blood pressure, in vivo. The 15-(S)-hydroxy configuration combined with the 8-iso configuration had the most potent constrictor activity, while the 15-(R)-hydroxy group negated this and even led, in the case of the natural configuration at C-8 and C-12, to vasodepression. 2. In vitro, the activity on the rat fundus and guinea-pig tracheal chain followed the same pattern. The 15-(S)-hydroxy derivatives were very much more potent than the 15-(R)-hydroxy derivatives at contracting the smooth muscle preparations. Uterine muscle appeared to be relaxed by the PGs with the natural configuration at C-8 and C-12, with the 15-(R)-hydroxy compound exhibiting greater activity. 3. Inhibition of ADP-induced rat blood platelet aggregation after "intra-arterial" administration was shown only by the derivatives with a single change in the natural configuration either at C-8 or at C-15. Additional changes either resulted in inactivity or, in the case of the 8,12-di-iso-15-(S)-hydroxy compound, even reversed the effect to aggregation. The inhibition of aggregation was long lasting with both the 8-iso-15-(S)-hydroxy derivative and the 8,12-nat-15-(R)-hydroxy derivative. In the case of the latter compound, GBR-30731, activity increased during the 30 min after administration. GBR-30731 deserves further investigation as a platelet aggregation inhibitor because of its relatively low smooth muscle stimulant (sometimes even relaxant effects) and its long lasting platelet aggregation inhibiting activity.

Animals↗
PubMed1985

Antagonism of prostaglandin-mediated responses in platelets and vascular smooth muscle by 13-azaprostanoic acid analogs. Evidence for selective blockade of thromboxane A2 responses.

Studies were undertaken to examine the pharmacological properties and stereochemical requirements of a limited series of prostanoic acid analogs for inhibition of arachidonic acid (AA) and/or endoperoxide (U46619)-mediated responses in human platelets and rat aorta. To assess the role of stereochemistry, a set of trans- and cis-isomers of 13-azaprostanoic acid (APA) and 11a-homo-13-azaprostanoic acid (HAPA) were prepared. Each prostanoic acid analog blocked AA- or U46619-induced aggregatory and secretory responses in platelets, and U46619-mediated contractions of rat aorta in a concentration-dependent manner (0.1 to 100 microM). The azaprostanoic acid analogs blocked responses to both inducers of platelet activation with IC50 values ranging from 3.4 to 27.5 microM. Trans-APA was about 2- to 3-fold more active as an antagonist of serotonin release induced by AA or U46619 than the remaining analogs. The rank order of inhibitory potency (IC50; microM) for these analogs against U46619-induced serotonin release in human platelets was trans-APA (3.4) greater than cis-APA (8.9) = cis-HAPA (8.7) = trans-HAPA (9.1). Concentrations of the prostanoic acid analogs required to block these responses to AA and U46619 were similar, and the highest concentration used (100 microM) did not modify AA-induced malondialdehyde production in human platelet preparations. In contrast, the isomers of APA and HAPA were equally active as antagonists of U46619-induced contractions of rat vascular tissue, possessing KB values varying from 7.1 to 13.2 microM. Each azaprostanoic acid analog shifted the concentration-response curve of U46619 in rat aorta to the right, indicating a competitive-type inhibition. In addition, the azoprostanoic acid analog (U51605) was a more potent competitive antagonist of U46619 in this preparation and possessed an average pKB value of 6.18. In summary, the results show that (1) expansion of the five-membered ring of APA to the six-membered ring analogs (HAPA) led to a retention of potent inhibitory activity against U46619 in human platelets and rat vascular smooth muscle, (2) the antiaggregatory and antisecretory actions of the azaprostanoic acid analogs were mediated by a blockade of the responses to AA and U46619, and not by an inhibition of AA metabolism, (3) the blocking activity for the APA isomers was stereoselective (trans greater than cis) whereas the isomers of HAPA were equally effective as inhibitors of platelet function; and (4) these azaprostanoic acid analogs act as selective endoperoxide (U46619)/thromboxane A2 antagonists in these two tissues.

Adult↗
PubMed1982

Metabolism of the prostaglandin fertility regulator sulprostone in monkeys.

The prostaglandin imide analog sulprostone (I) was labeled with tritium in the phenoxy ring to trace the fate of the prostanoic acid portion of the molecule and with carbon-14 in the methanesulfonimide moiety to trace the fate of that portion of the molecule. Disposition was studied after intravenous administration to female cynomolgus monkeys. The excretion and plasma pharmacokinetics of total radioactivity indicated that the prostanoic acid and methanesulfonimide moieties were disposed of differently, implying that hydrolysis of sulprostone was extensive and that the hydrolysis products were treated independently. The urinary excretion of tritium (prostanoic acid) was consistent with that observed for other prostaglandins. The urinary excretion and plasma pharmacokinetics of carbon-14 were consistent with those expected for methanesulfonamide. Urinary metabolites identified in 0-2 hr urine included a trace amount of unchanged drug, methanesulfonamide, and two products of beta-oxidation - the tetranor and dihydrotetranor prostanoic acids.

Animals↗
PubMed1996

Characterization of prostaglandin F2 alpha production in pregnant and cycling mice.

To clarify the regulation of prostaglandin F2 alpha (PGF2 alpha) production in vivo in mice during pregnancy and the estrous cycle, we injected [3H]PGF2 alpha i.v. into female mice and determined the structures of three urinary metabolites by gas chromatography-mass spectrometry. The compounds were 5,7,11-trihydroxy-tetranor-prosta-9-enoic acid (FUM-I), 5,7,11-trihydroxy-tetranor-prostanoic acid (FUM-II), and 5,7-dihydroxy-11-keto-tetranor-prostanoic acid (FUM-III). The major metabolite, FUM-III, increased four-fold at the term of pregnancy and transiently during diestrus of the estrous cycle. Consistent with the increase in FUM-III, immunoblot analysis with anti-bovine PGF synthase antiserum demonstrated that a 36-kDa protein band corresponding to PGF synthase increased in the uterus at late pregnancy and during diestrus. These results suggest that PGF2 alpha production may increase at term and change during the estrous cycle and is associated with an increase in uterine PGF synthase concentrations.

Animals↗
PubMed1979

13-Azaprostanoic acid: a specific antagonist of the human blood platelet thromboxane/endoperoxide receptor.

A newly synthesized 13-aza derivative of prostanoic acid (13-APA) specifically inhibited human platelet aggregation induced by arachidonic acid, prostaglandin H2, or the stable endoperoxide analog (15S)-hydroxy-9 alpha,11 alpha-)epoxymethano)-prosta-5Z,13E-dienoic acid. 13-APA also inhibited [14C]serotonin release in response to arachidonic acid, ADP, or thrombin, but did not inhibit primary aggregation induced by ADP or thrombin. 13-APA completely blocked prostaglandin H2-induced aggregation in indomethacin-treated resuspended platelets but did not inhibit thromboxane synthesis. We therefore conclude that 13-APA acts as a direct antagonist of the platelet thromboxane/endoperoxide receptor.

Adenosine Diphosphate↗
PubMed1985

Nonprotein sulfhydryls as possible components of the protective effect of rosaprostol on the rat gastric mucosa.

Experiments were designed to examine the possibility that nonprotein sulfhydryl groups of the gastric mucosa could participate in the protection of rat gastric mucosa by rosaprostol (the Na salt of 9-hydroxy-8,12 trans-19,20-bis-nor-prostanoic acid). Gastric mucosal lesions and the content of nonprotein sulfhydryls were evaluated after orally administered absolute ethanol. Pretreatment with rosaprostol by gavage prevented gastric lesions and reduced or prevented the decrease of mucosal nonprotein thiols. N-ethylmaleimide, a sulfhydryl blocker, worsened the ethanol-induced gastric lesions and lowered further the non protein thiols. Both variables were improved by the PG analogue and by PGE2. These results suggest a possible role of endogenous nonprotein sulfhydryl groups in the gastric protective effect of rosaprostol.

Animals↗
PubMed1979

Influence of the arachidonic acid cascade on the in vitro hepatic response to hypoxia.

Studies were undertaken to determine the effect of arachidonic acid, the precursor of bisenoic prostanoic acid derivatives, on the response of the isolated, perfused rabbit liver to hypoxia. Two and one half hours of severe hypoxia resulted in significant increases in hepatic vascular perfusion pressure, tissue wet weight, and the rates of cellular loss of lactic dehydrogenase, malic dehydrogenase, and acid phosphatase into the perfusing medium. Hypoxia also increased the rate of hepatic PGF2 alpha production by 25% after 2 1/2 hours (p less than 0.05, hypoxia vs sham). The addition of arachidonic acid (0.1 microgram/g/min for 150 minutes) to the perfusion medium of hypoxic livers significantly attenuated the changes in perfusion pressure, tissue wet weight, and loss of cellular enzymes. Arachidonic acid administration increased the rate of PGF2 alpha production by 100% (p less than 0.05, sham vs hypoxia + arachidonic acid) within 30 min after hypoxia and maintained this rate for the duration of the study. These results demonstrate that hypoxia mediated prostaglandin F2 alpha synthesis in the rabbit liver can occur in the absence of neural and blood borne components and that significant activation of the arachidonic acid cascade via the administration of exogenous arachidonic acid has a salutary effect on hepatic hemodynamics and cellular integrity during hypoxia.

Acid Phosphatase↗
PubMed1986

Prostaglandin D2 interacts at thromboxane receptor-sites on guinea-pig platelets.

The anti-aggregatory prostanoid, prostaglandin D2 (PGD2) does not completely inhibit ADP-induced aggregation of guinea-pig platelets and thus produces a bell-shaped dose-inhibition curve. The nature of this bell-shaped curve has now been investigated in guinea-pig platelet-rich plasma. Two selective thromboxane receptor antagonists, 13-aza-prostanoic acid (13-AZA; 16-64.4 microM) and BM 13.177 (5.9-29.8 microM), converted PGD2 to a full inhibitor of aggregation in a dose-related manner. The putative platelet PGD2 receptor antagonist, N-0164 (75 microM) also converted PGD2 to a full inhibitor of platelet aggregation. In contrast to 13-AZA and BM 13.177, higher concentrations of N-0164 (380 and 760 microM) caused a dose-related rightward shift of the PGD2 dose-inhibition curve. The thromboxane receptor antagonism of N-0164 was confirmed in studies in which the dose-aggregation curve to U-46619, a thromboxane mimetic, was competitively antagonized with a pA2 value of 4.67 and a slope of 1.13, comparable to that of 13-AZA. The results show that N-0164 acts as both a platelet PGD2 and thromboxane-receptor antagonist in both human and guinea-pig platelet-rich plasma. The results further indicate that PGD2 can interact at thromboxane receptors in guinea-pig platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗