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Biomedical subjects

M Hamberg

Publications and source records attributed to M Hamberg.

At least 127 records · Page 7Linked to original sources
PubMed1978

A method for measurement of platelet regeneration in man.

Platelet suspensions obtained at different time intervals following a single dose of oral aspirin were incubated with [1-(14)C]-arachidonic acid and the amount of [1-(14)C]thromboxane B2 formed was determined by a double isotope technique. Since aspirin is an irreversible inhibitor of platelet cyclooxygenase and since circulating platelets do not synthesize cyclooxygenase the rate of reappearance of active cyclooxygenase determined in this way was a measure of the rate of regeneration of functioning platelets. In two subjects the regeneration half-times were 4.2 and 4.8 days.

Aspirin↗
PubMed1978

Bronchial and cardiovascular actions of prostaglandin endoperoxides and an endoperoxide analogue.

Effects of PGG2, PGH2 and the endoperoxide analogue, EPA, on bronchial and vascular smooth muscle were studied in vivo and in vitro. In the cat PGG2, PGH2 and particularly EPA proved potent stimulators of airway resistance, and they were all significantly more active than PGF2 alpha. They also increased pulmonary vascular resistance but EPA alone was more active than PGF2 alpha. In guinea pigs EPA was 90--190 times more active than PGF2 alpha in increasing tracheal insufflation pressure. Human bronchi contracted in response to PGG2, PGH2 and EPA. PGG2 and PGH2 were equiactive with PGF2 alpha and EPA was more than 500 times as potent. PGG2 and PGH2 lowered systemic arterial blood pressure and increased heart rate in cats. They were as active or more active than PGE2, EPA, on the other hand, resembled PGF2 alpha in producing biphasic changes of blood pressure and heart rate or decrease of blood pressure and bradycardia in guinea pig and cat. The results obtained in this study indicate that PGG2, PGH2 and EPA are potent stimulators of bronchial and pulmonary vascular smooth muscle. The data are also consistent with the view that a significant proportion of effects resulting from prostaglandin generation in the lung is due to prostaglandin endoperoxides rather than primary prostaglandins.

Airway Resistance↗
PubMed1977

Glucocorticoid in inflammatory proliferative skin disease reduces arachidonic and hydroxyeicosatetraenoic acids.

Psoriasis is a prototype of several common, glucocorticoid responsive, inflammatory proliferative skin diseases. Within 28 hours, glucocorticoid reduced the increased concentration of free arachidonic acid in diseased tissue. This reduction was observed prior to visible improvement of disease and may be an important molecular mechanism for the therapeutic efficacy of glucocorticoids in psoriasis and similar inflammatory diseases.

Adolescent↗
PubMed1977

Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain.

Prostaglandin (PG) E2, D2, F2alpha and thromboxane B2 (TxB2) were determined in homogenates of rat brain by gas-chromatography--mass spectrometry. The level of PGD2 was 735 +/- 19 ng/g, of PGF2alpha 150 +/- 13 ng/g, of TxB2 112 ng/g and of PGE2 86 +/- 8 ng/g. The same relative proportions of cyclooxygenase products were found in incubates of unstimulated sliced rat brain. 14C-PGH2 was converted in high yield into PGD2 by enzyme(s) present in the soluble fraction of the homogenate. These results indicate that PGD2 is the major cyclooxygenase product in the central nervous system of the rat.

Animals↗
PubMed1977

Thromboxane A2: effects on airway and vascular smooth muscle.

Thromboxane A2, an unstable compound derived from prostaglandin G2, was generated by incubation of arachidonic acid with a suspension of human platelets. The activity of thromboxane A2 relative to that of prostaglandin H2 in causing contractions of a number of smooth muscle organs were as follows: rabbit aorta, 7-20; human umbilical artery, 9-60; and guinea pig trachea, 2-12. Intravenous injection of thromboxane A2 into anaesthetized quinea pigs was followed by a pronounced increase in the tracheal insufflation pressure, potency compared to prostaglandin H2, 31-45.

Animals↗
PubMed1977

Potentiation of itch and flare responses in human skin by prostaglandins E2 and H2 and a prostaglandin endoperoxide analog.

The itch and erythematous responses induced by intradermal injection of prostaglandin E2 (PGE2), the unstable prostaglandin endoperoxide PGH2 (t1/2 approximately 5 min at 37 degrees C) and the stable endoperoxide analog (15S)-hydroxy-9alpha, 11alpha-(epoxymethano)prosta-5,13-dienoic acid (EPA) were studied in volunteers. The compounds were given alone or in combination with histamine. All the compounds produced flare reaction in the skin; the order of potency was PGE2 greater than PGH2 greater than EPA. PGE2 and PGH2 evoked a sensation of itch in about half of the subjects whereas the same doses of EPA gave no itch response. In combination with histamine all compounds elicited itch of longer duration and flare of larger area than could be accounted for by simple additive effects of any released histamine. The results indicate that the PGs and PG intermediates formed in skin may potentiate the pruritogenic and flare-inducing effects of inflammagens in man.

Adolescent↗
PubMed1976

Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases.

Addition of arachidonic acid and homo-gamma-linolenic acid to a suspension of rabbit peritoneal neutrophils led to the synthesis of 5-L-hydroxy-6,8,11,14-eicosatetraenoic acid and 8-L-hydroxy-9,11,14-eicosatrienoic acid, respectively. Both hydroxy acids were found to be the main metabolites of their respective unsaturated C-20 fatty acid precursor, constituting more than 50% of the total substrate conversion. The formation of the two metabolites was not inhibted bb indomethacin, indicating that the enzymes involved were unrelated to the prostaglandin synthetase system. The presence in the two compounds of a hydroxyl group alpha to a pair of conjugated cis/trans double bonds suggested that they were formed by action of lipoxygenease(s).

8,11,14-Eicosatrienoic Acid↗
PubMed1976

Antagonism of the prostaglandin endoperoxide imhibition of hormone-stimulated adenylate cyclase by guanosine triphosphate and 5'-guanylyl-imidodiphosphate.

The prostaglandin endoperoxide prostaglandin H2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid) inhibits basal and hormone-stimulated adenylate cyclase in fat cell ghosts. This inhibition by prostaglandin H2 has been found to be antagonized by GTP and Gpp(NH)p. Dose response studies have shown GTP and Gpp(nh)p to be maximally effective at 3.3 muM, the lowest concentration tested. Although the system is exceedingly sensitive to modulation by GTP or Gpp(NH)p UTP, CTP, GMP, and cyclic GMP did not antagonize the antihormone activity of prostaglandin H2. Kinetic studies indicate that the GTP or Gpp(NH)p antagonism of prostaglandin H2 is observable on initial rates of cyclic AMP synthesis, and persists throughout the adenylate cyclase measurements. Preincubation of fat cell ghosts with GTP followed by washing and resuspension results in a prostaglandin H2-sensitive adenylate cyclase system. However, the same preincubation experiment with Gpp(NH)p produces an irreversible antagonism of the prostaglandin H2 inhibition of hormone-stimulated adenylate cyclase. It is suggested that prostaglandin H2 stabilizes the fat cell adenylate cyclase system in a state that is resistant to hormone stimulation, and GTP or Gpp(NH)p overcome this stabilization.

Adenylyl Cyclases↗
PubMed1976

Metabolism of 8,11,14-eicosatrienoic acid in human platelets.

The following labeled compounds were isolated and identified after incubation of 8,11,14-eicosatrien [1-14C] oic acid with human platelets: 12-L-hydroxy-8,10,14-eicosatrienoic acid, 8,11,12-trihydroxy-9,14-eicosadienoic acid, 8,9,12-trihydroxy-10,14-eicosadienoic acid, 12-L-hydroxy-8,10-heptadecadienoic acid, prostaglandin E1, prostaglandin D1, and 8-(1-hydroxy-3-oxopropyl)-9,12-dihydroxy-10-heptadecenoic acid (thromboxane B1).

8,11,14-Eicosatrienoic Acid↗
PubMed1976

Biosynthesis of prostaglandin F2alpha from arachidonic acid and prostaglandin endoperoxides in the uterus.

Formation of prostaglandin F2Alpha in the cow and guinea pig uterus microsomes was studied using 14C-labeled arachidonic acid and prostaglandin H2. The total conversion of arachidonic acid was of a low order and underwent fluctuations during the estrous cycle of the guinea pig, being highest towards the end of the cycle. Injections of beta-estradiol-3-benzoate also resulted in higher activity of the uterine prostaglandin synthetase. The uterine prostaglandin synthesizing system appeared to differ in several respects from that present in seminal vesicles, with regard to the proportions of the products formed and the effects of various agents, e.g. reduced glutathione. An inhibiting factor which supressed the fatty acid cyclo-oxygenase was found to be present in uterine preparations. Prostaglandin endoperoxide (prostaglandin H2) was very efficiently reduced to prostaglandin F2alpha by cow and guinea-pig uterus microsomes. Prostaglandin G2 also gave rise to prostaglandin F2alpha. Prostaglandin E2, on the other hand, was not reduced. Both the inhibiting factor and the endoperoxide reducing activity are likely to be parts of a highly specialized mechanism that modulates prostaglandin F2alpha formation in the uterus.

Animals↗
PubMed1976

On the formation of thromboxane B2 and 12l-hydroxy-5,8,10,14-eicosatetraenoic acid (12 ho-20:4) in tissues from the guinea pig.

Homogenates of tissues from the guinea pig were incubated at 37 degrees C for 30 min and the amounts of thromboxane B2 and 12L-hydroxy-5,8,10,14-eicostetraenoic acid (12ho-2-:4) formed from endogenous arachidonic acid were determined by multiple-ion analysis. Lung and spleen homogenates produced 7146 +/- 500 ng/g and 3046 +/- 542 ng/g, respectively, of thromboxane B2 and 15 122 +/- 3536 ng/g and 29 516 +/- 1966 ng/g, respectively, of 12ho-20:4. The amounts of both compounds in homogenates of kidney, stomach, liver, heart and whole blood were at least 10-times lower than those found in lung and spleen. 5,8,11,14-Eicostetraynoic acid and nordihydroguaiaretic acid inhibited 12ho-20:4 formation in spleen homogenates whereas indomethacin and arachidonic acid stimulated it.

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

Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides.

The microsomal fraction of horse and human platelets contains an enzyme which converts prostaglandin cyclic endoperoxides (PGG2 or PGH2) to a substance which is much more potent in contracting strips of rabbit aorta. This substance has the same characteristics as thromboxane A2, and can be distinguished from other products of arachidonic acid metabolism by differential bioassay.

Aorta↗
PubMed1976

Isomerization of prostaglandin H2 into prostaglandin D2 in the presence of serum albumin.

The prostaglandin endoperoxide, prostaglandin H2, decomposes in aqueous media mainly into prostaglandin E2. This paper shows that in the presence of serum albumin from a number of species prostaglandin H2 decomposes mainly into prostaglandin D2, an isomer of prostaglandin E2. The effect on endoperoxide decomposition exerted by serum albumin may well have physiological significance since intace endoperoxides can be released from tissues and since the biological properties of prostaglandins E2 and D2 are quite different.

Animals↗