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Biomedical subjects

B Samuelsson

Publications and source records attributed to B Samuelsson.

At least 307 records · Page 17Linked to original sources
PubMed1975

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

The 9,11-azo-prostanoid III [(5Z, 9alpha, 11alpha, 13E, 15S)-9, 11-azo-15-hydroxyprosta-5,13-dienoic acid] has been obtained by synthesis and tested for biological activity in systems which are responsive to the prostaglandin endoperoxides PGH2 (I) and PGG2 (II). The azo analog III is a powerful mimic of these endoperoxides with reference to platelet aggregation and release of serotonin when added to human platelet-rich plasma. The analog III is substantially more active (about 7 fold) than PGG2 in stimulating muscle contraction in the isolated rabbit aorta strip. The very great stability of III relative to PGH2 and PGG2 and its potency as a mimic of these important substances suggest that this azo analog will be of considerable value in future studies of the prostaglandin endoperoxides.

Aorta↗
PubMed1975

Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets.

Material causing contraction of the isolated rabbit aorta (rabbit aorta contracting substance, RCS) was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation. Prostaglandin endoperoxides (prostaglandins G2 and/or H2) were found both in the perfusate of guinea pig lung (1-3 ng/ml) and in the medium collected after platelet aggregation (13-37 ng/ml). The contractile response of the isolated rabbit aorta to the pure prostaglandins G2 and H2 was also determined. These data combined with the quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aorta contracting activity was due to the prostaglandin endoperoxides. The major part of the activity consisted of very unstable material. The half life of this material was about 30 s at 37 degrees whereas at this temperature the prostaglandin endoperoxides had a half life of about 5 min.

Animals↗
PubMed1975

Prostaglandins.

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Adipose Tissue↗
PubMed1974

Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins.

Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163-2175 ng/ml of HETE, 1129-2430 ng/ml of HHT, and 998-2299 ng/ml of PHD. The amount of PGG(2) (prostaglandin G(2)) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477-5480 ng/ml. In contrast, the amounts of PGE(2) (prostaglandin E(2)) and PGF(2alpha) (prostaglandin F(2alpha)) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins. Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal [Hamberg, M., Svensson, J., Wakabayashi, T. & Samuelsson, B. (1974) Proc. Nat. Acad. Sci. USA 71, 345-349] that the anti-aggregating effect of aspirin is through inhibition of PGG(2) formation.

Arachidonic Acids↗
PubMed1974

Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation.

Incubation for a short time of arachidonic acid with the microsomal fraction of a homogenate of the vesicular gland of sheep in the presence of 1 mM p-mercuribenzoate followed by extraction and silicic acid chromatography yielded two prostaglandin endoperoxides. The structures of these compounds, i.e., 15-hydroperoxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid (prostaglandin G(2)) and 15-hydroxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid (prostaglandin H(2)), were assigned mainly by a number of chemical transformations into previously known prostaglandins. The new prostaglandins were 50-200 times (prostaglandin G(2)) and 100-450 times (prostaglandin H(2)) more active than prostaglandin E(2) on the superfused aorta strip. The half-life of the prostaglandin endoperoxides in aqueous medium (about 5 min) was significantly longer than that of "rabbit aorta-contracting substance" released from guinea pig lung, indicating that none of the prostaglandin endoperoxides is identical with this factor. Addition of 10-300 ng/ml of the endoperoxides to suspensions of washed human platelets resulted in rapid aggregation. Furthermore, platelet aggregation induced by thrombin was accompanied by release of material reducible by stannous chloride into prostaglandin F(2alpha), thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation.

Animals↗
PubMed1974

Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets.

Arachidonic acid incubated with human platelets was converted into three compounds, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, 12L-hydroxy-5,8,10-heptadecatrienoic acid, and the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid. The formation of the two latter compounds from arachidonic acid proceeded by pathways involving the enzyme, fatty acid cyclo-oxygenase, in the initial step and with the prostaglandin endoperoxide, PGG(2), as an intermediate. The first mentioned compound was formed from 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid, which in turn was formed from arachidonic acid by the action of a novel lipoxygenase. Aspirin and indomethacin inhibited the fatty acid cyclo-oxygenase but not the lipoxygenase, whereas 5,8,11,14-eicosatetraynoic acid inhibited both enzymes. The almost exclusive transformation of the endoperoxide structure into non-prostaglandin derivatives supports the hypothesis that the endoperoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions. The observed transformations of arachidonic acid in platelets also explain the aggregating effect of this acid.

Arachidonic Acids↗
PubMed1973

Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis.

An earlier proposed endoperoxide intermediate in the biosynthesis of prostaglandins was detected in short-time incubations of arachidonic acid with the microsomal fraction of homogenates of sheep vesicular glands. Conversion of the endoperoxide into prostaglandin E(2) was stimulated by reduced glutathione but suppressed by p-mercuribenzoate and N-ethylmaleimide. The methyl ester of an unknown compound was isolated by solvent extraction and thin-layer chromatography after short-time incubation of arachidonic acid with the microsomal fraction and p-mercuribenzoate. This derivative was identical to the methylester of the endoperoxide, as shown by its conversion into the methyl esters of 11-dehydroprostaglandin F(2alpha) and prostaglandin E(2) by spontaneous rearrangement and its conversion into the methyl ester of prostaglandin F(2alpha) by mild chemical reduction. The smooth muscle-stimulating activity of the endoperoxide ester on the isolated rabbit aortas trip was 4- to 8-times higher than that of the methyl ester of prostaglandin E(2).

Animals↗