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Biomedical subjects

M Hamberg

Publications and source records attributed to M Hamberg.

At least 145 records · Page 8Linked to original sources
PubMed1976

A comparison of the vasodepressor effects of the cyclic effects of the cyclic endoperoxides PGG, and PGH2 with those of PGD2 and PGE2 in hypertensive and normotensive rats.

The vasodepressor actions of the cyclic endoperoxides PGG2 and PGH2 were compared with those of their products PGD2 and PGE2 using anaesthetised normotensive and genetically hypertensive rats. Given into the aortic arch of normotensives PGE2 was approximately 6 times more potent than PGH2 and 11 times more potent than PGG2 and PGD2. Hypertensive animals were 1.5-10 times more sensitive than normotensives to the depressor effects of PGG2 and PGH2, but their sensitivity to either PGD2 or PGE2 was similar. Thus in hypertensives the endoperoxides may be converted more readily to PGE2 and other products. In both types of rat PGG2 and PGH2 given intravenously were as active or more active than after intra-arterial. Therefore PGG2 and PGH2 may be converted more readily to more active products during passage through the lungs but whereas small doses of PGE2 are almost completely eliminated large doses may saturate uplmonary removal mechanisms.

Animals↗
PubMed1976

Metabolism and effect of prostaglandin H2 in adipose tissue.

Prostaglandin H2 (PGH2) inhibited noradrenaline induced cyclic AMP accumulation in isolated rat fat cells in a dose-dependent manner. IC50 was 10-25 ng/ml both in the absence and in the presence of theophylline. The degree of inhibition produced by PGH2 increased with time of incubation. A stable PGH2 analog did not inhibit cyclic AMP accumulation. PGH2 was rapidly converted by isolated fat cells to PGD2, PGE2 and PGF2alpha' but no formation of thromboxane B2 was found either in vitro or in vivo. PGE2 was a more potent inhibitor than PGH2 of noradrenaline induced cyclic AMP accumulation. PGD2 enhanced cyclic AMP accumulation in a limited concentration interval, while PGF2alpha was essentially uneffective. Our results suggest that PGH2 is an inhibitor of cyclic AMP formation in isolated rat fat cells only after conversion to PGE2. A physiological role for PGH2 as a modulator of lipolysis is considered unlikely.

Adipose Tissue↗
PubMed1976

Thromboxane A2 and prostaglandin H2: potent stimulators of the swine coronary artery.

Thromboxane A2 was generated by incubation of arachidonic acid with a suspension of human platelets. The filtrate contained 266 +/- 46 ng/ml (n=10) of thromboxane A2 and 25 ng/ml or less of prostaglandin endoperoxides (prostaglandins G2+H2). Thromboxane A2 was 2-10 times more potent than prostaglandin H2 and 9-102 times and 26-308 times more potent than prostaglandins E2 and F2alpha, respectively, in causing contractions of the superfused swine coronary artery.

Animals↗
PubMed1976

Effects of stimulation and inhibition of the renal prostaglandin synthetase system on renin release in vivo and in vitro.

1. The prostaglandin precursor arachidonic acid (C20:4) increases plasma renin activity in the rabbit and rat when it is infused into the renal arteries. 2. The increase in plasma renin activity after C20:4 in rats is not changed by volume expansion. 3. The inhibitor of prostaglandin synthesis indomethacin decreases plasma renin activity in the rabbit. 4. The increase plasma in renin activity after total renal ischaemia is abolished by pretreatment with indomethacin. 5. C20:4 increases dose- and time-dependent renin release from slices of rabbit kidney cortex. 6. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment in vivo, and addition to the incubation medium, reduces basal as well as C20:4-stimulated renin release in vitro. 7. The stimulating effect of C20:4 on renin release is assumed to be caused directly by formation of prostaglandin endoperoxides in the kidney cortex and not by prostaglandins since in vitro a natural prostaglandin endoperoxide (PGG2) and two stable synthetic prostaglandin endoperoxide analogues (EPA I and EPA II) do increase the release of renin, but PGE2 has no effect and PGF2alpha inhibits renin release.

Animals↗
PubMed1976

Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery.

The effects on the isolated human umbilical artery (HUA) of the recently isolated endoperoxide intermediates in prostaglandin (PG) biosynthesis, PGG2 and PGH2, were studied. Both endoperoxides were potent contractors of the artery strips, the threshold concentrations being 3 (1-4) ng/ml for PGG2 and 1 (1-12) ng/ml for PGH2, as compared with 200 (40-400) ng/ml for PGE2. The hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2), a metabolite of PGG2, appeared in the bath medium indicating PG and thromboxane generation in the isolated HUA. The formation of thromboxane B2 was inhibited by indomethacin (8-40 mug/ml) and by eicosa-5,8,11,14-tetraynoic acid (ETA) (25 mug/ml), ETA also inhibited the contractile responses to both endoperoxides. The results support the view that local generation of PGs might be involved in the closure of the HUA at birth.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1976

On the formation and effects of thromboxane A2 in human platelets.

Incubation of arachidonic acid and prostaglandin G2 with a suspension of human platelets led to formation of an unstable (t1/2, 41+/-7 s) compound, thromboxane A2. Thromboxane A2 induced irreversible aggregation of washed platelets and of platelets in platelet-rich plasma and caused release of serotonin and ADP from platelets in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1976

Prostaglandin biosynthesis in the human umbilical cord.

The content of prostaglandins (PGs) in homogenates of arteries, connective tissue from human umbilical cords, and the capacity for biosynthesis of PGs in these tissues were studied. Lipid extracts were prepared and subjected to chromatography on silicic acid columns. PGs were eluted by ethyl acetate after elution with ethyl acetate-benzene (1:9) and determined by bioassay. For studies of the content of PGs, the cords were immediately frozen after delivery and homogenized in cold ethanol. Cords taken at vaginal deliveries contained amounts equivalent to approximately 700 ng prostaglandin E2/g dry weight and cords taken at caesarean sections about 450 ng/g. After homogenization and incubation of arteries in potassium phosphate buffer at 37 degrees C for 30 min the PG content increased from about 80 to 200 ng/g. Addition of arachidonic acid increased the biosynthesis fivefold. Indomethacin inhibited it. Most of the smooth muscle stimulating activity of the homogenated cords was due to prostaglandin E compounds, but smooth muscle stimulating material similar to prostaglandin F1alpha and F2alpha was also present. Prostaglandin E2 was conclusively identified by gas chromatography -- mass spectrometry. The findings are compatible with the view that local biosynthesis of PGs is very active in the human umbilical cord after delivery.

Arachidonic Acids↗
PubMed1976

Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides.

The mechanism by which renal prostaglandins stimulate renin secretion in vivo is unknown. In this in vitro study we measured the effects of activation of the prostaglandin (PG) system on renin release from slices of rabbit renal cortex. The PG precursor arachidonic acid (C20:4), a natural PG endoperoxide (PGG2), two stable synthetic PG endoperoxide analogues (EPA I and II), PGE2, PGF2alpha, and two different PG synthesis inhibitors [indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA)] were used to evaluate the possibility of a direct action of the cortical PG system on renin secretion. Renin release increased significantly with time after addition of C20:4, PGG2, EPA I, and EPA II to the incubation medium. Stimulation of renin release was se-related for C20:4 in concentrations of 0.6 to 4.5 X 10(-6) M, for EPA I in concentrations of 0.7 to 2.8 X 10(-6) M, and for EPA II in concentrations of 1.4 to 14.0 X 10(-6) M. Indomethacin (10(-4) M) and ETA (10(-4) M) significantly decreased basal renin release as well as the renin release stimulated by C20:4 and EPA I. PGE2(10(-12) to 10(-6) M) had no effect on renin release, whereas PGF2alpha (10(-12) to 10(-6) M) decreased renin release in a dose-dependent manner. These data raise the possibility of a direct action of the renal cortical PG system on renin secretion. The results further indicate that stimulation of renin release by C20:4 may depend more specifically on the action of PG endoperoxides than on the primary prostaglandins.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1976

Involvement of endoperoxides and thromboxanes in anaphylactic reactions.

Our recent work on prostaglandin endoperoxides in the lung has shown that: 1. The endoperoxides were 5 to 10 times more potent than PGF2alpha in an in vitro preparation of respiratory smooth muscle, i.e., the guinea pig trachea. 2. The endoperoxides were 5 to 10 times more potent than PGF2alpha in causing an increase in tracheal insufflation pressure in the anaesthetized, artificially ventilated guinea pig. 3. Endoperoxides formed from exogenous arachidonic acid in homogenates of guinea pig lung and in intact guinea pig lung were converted to a large extent into metabolites different from the classical prostaglandins, i.e., thromboxane B2 (8-(1-hydroxy-3-oxopropyl)-9-12L-dihydroxy-5,10-heptadecadienoic acid) and HHT (12L-hydroxy-5,8,10-heptadecatrienoic acid). 4. Injection of antigen into sensitized guinea pig lungs caused a significant release of the endoperoxide metabolite, thromboxane B2. PGF2alpha has previously been implicated to be involved in anaphylaxis (14). The findings described above show that the prostaglandin endoperoxides are important not only as precursors of PGF2alpha but also through their own effects on airway smooth muscle. Furthermore, the release of thromboxane B2 indicates that its immediate precursor, the biologically active thromboxane A2 is also formed in this system (15). This compound, which has a half-life of 30 to 40 sec causes platelet aggregation and contraction of the isolated rabbit aorta (15). Work is in progress to study the respiratory effects of thromboxane A2 and its possible role in anaphylactic reactions.

Anaphylaxis↗
PubMed1975

Inhibition of basal and hormone-stimulated adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide prostaglandin H2.

The prostaglandin endoperoxide PGH2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid), at a concentration of 2.8 x 10(-5) M inhibited basal adenylate cyclase activity 11% and epinephrine-stimulated activity 30 to 35%. PGH2 inhibited epinephrine-stimulated enzyme activity in the presence of 10 mM theophylline, 2.5 mM adenosine 3':5'-monophosphate (cAMP), or in the absence of inhibitors or substrates of the cAMP phosphodiesterase. When the cAMP phosphodiesterase was assayed directly using 62 nM and 1.1 muM cAMP, PGH2 did not affect the 100,000 x g particulate cAMP phosphodiesterase from fat cells. The inhibition of adenylate cyclase by PGH2 was readily reversible. A 6-min preincubation of ghost membranes with PGH2, followed by washing, did not alter subsequent epinephrine-stimulated adenylate cyclase activity. During epinephrine stimulation, the PGH2 inhibition was apparent on initial rates of cAMP synthesis, and the addition of PGH2 to the enzyme system at any point during an assay markedly reduced the rate of cAMP synthesis. Between 2.8 x 10(-7) M and 2.8 x 10(-5) M, PGH2 inhibited epinephrine-stimulated enzyme activity in a concentration-dependent manner. The stimulation of adenylate cyclase by thyroid-stimulating hormone, glucagon, and adrenocorticotropic hormone as well as by epinephrine was antagonized by PGH2, suggesting that PGH2 may be an endogenous feedback regulator of hormone-stimulated lipolysis in adipose tissue.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Decomposition of unsaturated fatty acid hydroperoxides by hemoglobin: Structures of major products of 13L-hydroperoxy-9,11-octadecadienoic acid.

13L-hydroperoxy-9, 11-octadecadienoic acid was decomposed rapidly in the presence of hemoglobin. The product consisted of five major compounds, i.e. 13-keto-9, 11-octadecadienoic acid, 13L-hydroxy-9, 11-octadecadienoic acid, erythro-11-hydroxy-12, 13-epoxy-9-octadecenoic acid, threo-11-hydroxy-12, 13-epoxy-9-octadecenoic acid, and 9 DL-hydroxy-12, 13-epoxy-10-octadecenoic acid.

Animals↗