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E Granström

Publications and source records attributed to E Granström.

At least 55 records · Page 3Linked to original sources
PubMed1982

Species differences in circulating prostaglandin metabolites. Relevance for the assay of prostaglandin release.

The profiles of circulating metabolites of prostaglandin F2 alpha were investigated in a number of species, viz. rat, rabbit, guinea pig, cattle and sheep. The aim of the study was to identify in each animal major plasma metabolites that outlast the initially formed, short-lived 15-keto-13, 14-dihydroprostaglandin F2 alpha and might thus serve as better parameters for monitoring prostaglandin production in vivo. Tritium-labeled prostaglandin F2 alpha was injected intravenously and frequent blood samples were collected. The metabolic profiles at different stages were visualized using two-dimensional thin-layer chromatography and autoradiography. Identification of circulating products was achieved by comparison with reference compounds using several chromatographic methods, and by gas chromatography-mass spectrometry in cases where larger amounts of the prostaglandin had been administered. In the rabbit a similar study was also done with tritium-labeled prostaglandin E2. Certain species differences were seen in the removal of labeled compounds from the circulation, the elimination being most efficient in the guinea pig. Further differences were seen in the profiles of circulating prostaglandin metabolites. The first appearing major prostaglandin F2 alpha metabolite was always 15-ketodihydroprostaglandin F2 alpha. However, this compound was later replaced in the circulation by a number of more degraded products, the profiles of which were relatively typical for each species. Thus, in cattle, rat and guinea pig, the earliest-formed metabolites, 15-ketodihydroprostaglandin F2 alpha and its tetranor counterpart, 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprostanoic acid, remained comparatively prominent plasma products, whereas highly polar dicarboxylic acids rapidly dominated the metabolite spectrum in the ovine and lapine circulation. These differences were further supported by separate kinetic experiments, using unlabeled prostaglandin F2 alpha and radioimmunological determination of formed products. These latter experiments also demonstrated further pronounced species differences in the rat of elimination of the different prostaglandin metabolites. A considerable interconversion between prostaglandin E and F compounds was also demonstrated in some species. In conclusion, the traditional prostaglandin parameters in plasma, the 15-ketodihydrometabolites, were found not to be the best parameters in all species. It is suggested that species differences in prostaglandin metabolism are taken ito consideration when the optimal analytical protocol is sought for future biological studies. Some alternatives are suggested in the present paper.

Animals↗
PubMed1982

Profiles of prostaglandin metabolites in the human circulation. Identification of late-appearing, long-lived products.

The pattern of metabolites appearing in the circulation after intravenous injection of [9 beta-3H]prostaglandin F2 alpha was investigated in the human. Analysis of profiles of products was performed by two-dimensional TLC and autoradiography. Identification of labeled metabolites was accomplished by comparing their chromatographic behaviour with reference compounds in several chromatographic systems. After injection of [9 beta-3H]prostaglandin F2 alpha the initially formed metabolite was 15-keto-13,14-dihydroprostaglandin F2 alpha. However, this compound only dominated the spectrum of metabolites during the first few minutes, and several more polar products soon appeared. About 20 min after the injection the most prominent metabolite was 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprostane-1,16-dioic acid, which remained the dominating plasma compound and was also the major metabolite in urine. Several other highly oxidized products were also identified in plasma. Also these metabolites appeared later and remained longer in the circulation than the initially formed 15-ketodihydro metabolite. Our findings suggested that the more degraded metabolites might serve as more reliable plasma parameters for monitoring prostaglandin production than the traditional parameter, 15-ketodihydroprostaglandin F2 alpha. This hypothesis was supported by radioimmunoassay of metabolite levels in plasma appearing after either exogenous (intravenous administration) or endogenous prostaglandin F2 alpha (late human pregnancy and parturition). In all cases studied, the tetranor metabolites remained elevated in the circulation for several hours, in contrast to their precursor, 15-ketodihydroprostaglandin F2 alpha, which disappeared rapidly.

Autoradiography↗
PubMed1982

Effect of leucotrienes C4, D4, prostacyclin and thromboxane A2 on isolated human cerebral arteries.

The effects of leucotrienes C4 (LTC4), D4 (LTD4), Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were studied on superfused human cerebral artery strips. LTC4 and LTD4 neither contracted nor relaxed the strips. PGI2 caused a dose-dependent relaxation from 0.2 nmol to 0.8 nmol. When given simultaneously with a vasoconstrictor substance, PGI2 had an almost complete inhibitory effect. TXA2 caused a dose-dependent contraction from 0.03 nmol to 0.15 nmol. Also, TXA2 was more potent than 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) with a contraction threshold of about 0.1 nmol. Prostaglandin E1 (PGE1), H2 (PGH2), and F2a (PGF2a) had contraction thresholds of about 1 nmol. Only a stable endoperoxide analogue (EPA), was more potent than TXA2, with a contraction threshold of 0.005 nmol. The possible role of these substances in producing ischaemic manifestations after subarachnoidal haemorrhage (SAH) is discussed.

Aged↗
PubMed1980

Chemical instability of 15-keto-13,14-dihydro-PGE2: the reason for low assay reliability.

The spontaneous degradation of 15-keto-13,14-dihydro-PGE2 was studied under various conditions. In aqueous media, dehydration rapidly occurred, particularly at high or very low pH. The acid catalyzed dehydration product was identified as 15-keto-13,14-dihydro-PGA2. This compound was also formed at alkaline pH, however, at higher pH a bicyclic compound, 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2, was formed in addition (cf. Fig. 1). The amounts of the latter compound increased with time and with increasing pH. In samples containing albumin, 15-keto-dihydro-PGE2 was degraded even more rapidly than in buffer of the same pH. In addition to the formation of the dehydration products, a considerable part of the metabolite was bound to albumin to yield water soluble adducts. A similar binding occurred to a low molecular weight fraction of plasma. The compound that was bound was 15-keto-dihydro-PGA2, whereas both 15-keto-dihydro-PGE2 and the bicyclic product were relatively inert in this respect. Due to its chemical stability, the bicyclic degradation product, 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2, is suggested as a suitable target for measurements instead of the labile parent compound, 15-keto-dihydro-PGE2, or the reactive dehydration product, 15-keto-dihydro-PGA2.

Acids↗
PubMed1980

Interactions of prostaglandin H2 and thromboxane A2 with human serum albumin.

The present report describes the interactions of human plasma proteins with the unstable endoperoxide, prostaglandin H2 and thromboxane A2, generated by incubation of platelets with prostaglandin H2 or arachidonic acid. It was found that both compounds reacted very rapidly with plasma proteins to form covalently bound derivatives. The major reacting plasma protein was human serum albumin. Depending on conditions, 20-40% of added prostaglandin H2 and 50-80% of generated thromboxane were bound to proteins. This reaction of both prostaglandin H2 and thromboxane A2 prevents their detection by classical analytical methods. The protein binding of thromboxane was more pH-sensitive than the binding of prostaglandin H2. The reactions cause reduced levels of both endoperoxide and thromboxane B2 in suspensions of washed platelets using human serum albumin as compared to buffer. It was also shown that the half-life of prostaglandin H2 was considerably reduced in the presence of albumin.

Arachidonic Acids↗
PubMed1979

Efflux of cyclic AMP, prostaglandin E2 and F2 alpha and thromboxane B2 in leg lymph of rabbits after scalding injury.

Leg lymph was collected from pentobarbital anaesthetized rabbits before and after scalding injury of the paw (75 degrees C for 20 s), and the contents of cyclic AMP (cAMP), prostaglandin E2 (PGE2) and PGF2 alpha and thromboxane B2 (TXB2) in lymph were determined. After injury lymph flow increased about four times. The maximal rate of flow was found between 30 and 60 min after scalding. The efflux of cAMP and immunoreactive iPGE2, iPGF2 alpha and iTXB2 also increased. The maximum values were detected at approximately 0-30, 30-60, 30-60 and 180-240 min, respectively, after the injury. The output of cAMP, iPGE2 and iPGF2 alpha and iTXB2 in lymph of the contralateral non-scalded paw remained low throughout the experiments. When rabbits were injected with indomethacin (2.5 mg/kg) or diclofenac sodium (2.5 mg/kg) immediately after the scalding injury, the efflux of cAMP, iPGE2 and iPGF2 alpha were low. Lymph flow was markedly reduced after treatment with diclofenac sodium; treatment with indomethacin did not significantly affect lymph flow. The results suggest a prostaglandin-dependent formation of cAMP following scalding injury which may be related to the initial responses to scalding.

Animals↗