Search PubMed⌕ Search

Biomedical subjects

E Rosengren

Publications and source records attributed to E Rosengren.

At least 91 records · Page 5Linked to original sources

Lithium lowers renal, cardiac and splenic ornithine decarboxylase activity in mice.

A single i.p. injection of lithium chloride (5-7.5 mumoles/g b.wt) in mice caused a 70-80% decrease in renal, cardiac and splenic ornithine decarboxylase (ODC) activity within 1 h, whereas pulmonary ODC activity was unaffected. Lithium chloride did not have any effect on ODC activity in vitro when added to homogenates of the tissues studied. We suggest that the effect of lithium on ODC activity is not direct, but mediated via e.g. hormonal or nervous influence.

Animals↗

Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species.

The 5-S-cysteinyl derivatives of dopamine, dopa (3,4-dihydroxyphenylalanine) and dopac (3,4-dihydroxyphenylacetic acid) were synthesized and used as reference compounds in high performance liquid chromatography analyses of extracts from various brain regions of eight mammalian species. All three metabolites were detected in the brains of all the species studied. The regional distribution of the metabolites was similar to that of dopamine; the metabolite concentrations ranged from less than 0.1 percent to more than 1 percent of the dopamine level, the highest ratios generally being found in substantia nigra. It is suggested that the 5-S-cysteinyl catechol metabolites have been formed after autoxidation of catechols to quinones and subsequent coupling to glutathione. The adduct thus formed is finally split by peptidases to yield the 5-S-cysteinyl derivatives.

Animals↗

Histamine storage and formation in canine gastric mucosa--effect of pentagastrin stimulation.

Histamine storage and formation in the dog gastric mucosa were studied during basal conditions and after pentagastrin stimulation. Histamine formation (histidine decarboxylase activity), histamine content as well as the density of mast cells of the oxyntic gland mucosa were evenly distributed. Histamine content of the mucosa was significantly correlated to the density of mucosal mast cells. In the basal secretory state, histamine formation and histamine content of the oxyntic gland mucosa were of the same magnitude as in the antral mucosa. Pentagastrin stimulation induced a small but significant decrease in histamine content of the oxyntic gland mucosa and a subsequent acceleration in the rate of amine formation. Neither histamine content nor histidine decarboxylase activity of the antral mucosa was affected by pentagastrin infusion.

Animals↗

Distribution of ornithine decarboxylase in ovaries of rat and hamster during pro-oestrus.

The biosynthesis of polyamines is dramatically increased in the ovaries of rat and hamster during the evening of pro-oestrus. In an attempt to shed some light on the physiological function of this biosynthesis ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the biosynthesis of the polyamines, was immunohistochemically localized in the ovaries from rat and hamster during pro-oestrus. At dioestrus, only a few immunoreactive cells were found in the ovaries. During the evening of pro-oestrus, on the other hand, numerous immunoreactive cells were observed in the ovaries. These cells were confined to the internal thecal layer of Graafian as well as smaller follicles and to the interstitial tissue of the ovary. The granulosa cells appeared to be devoid of immunoreactive ODC. The hamster ovary, which during this time exhibited considerably higher levels of ODC activity than the ovaries from the rat, did accordingly contain more immunoreactive cells than the rat ovary.

Animals↗

Polyamine levels in human gastric carcinoma.

The results of experiments from several cell systems support the hypothesis that a connection exists between increased biosynthesis of polyamines (putrescine, spermidine, and spermine) and cellular growth. We have studied the polyamine levels and the activity of ornithine decarboxylase (a rate-limiting enzyme in mammalian polyamine synthesis) in human gastric carcinoma. Putrescine and spermidine levels were significantly elevated as compared with corresponding 'normal' gastric mucosa. The enzyme activity was also higher in neoplastic tissue, but the difference did not reach statistical significance. The present results may be interpreted to support the suggested role of polyamines in rapid tissue growth as represented by human gastric carcinoma.

Aged↗

Oxidation of dopa in the skin of black and albino mice.

The dopa oxidase activity of tyrosinase in the skin from albino and black mice was assayed using a technique based on the formation of two diastereomers of 5-S-cysteinyldopa when incubating tissue extracts with both L-dopa and D-dopa as substrates in the presence of cysteine. The amounts of 5-S-L-cysteinyl-L-dopa and 5-S-L-cysteinyl-D-dopa formed were then determined. In the extract from black mouse skin the L-L-diastereomer was produced in more than ten times the amount of the L-D-diastereomer. This stereospecific dopa-oxidation is indicative of the presence of tyrosinase and corresponds well with earlier determinations of the rates of oxidation for human tyrosinase, using L-dopa and D-dopa as substrates. Stereospecific dopa oxidation was absent in albino skin, and the nonspecific dopa-oxidation was two orders of magnitude less than the dopa oxidation in black skin. The study demonstrates the lack of tyrosinase activity in albino skin, and quantifies the non-specific dopa oxidation. The lack of tyrosinase activity in the eluates from albinotic skin was found not to be due to the presence of a tyrosinase inhibitor.

Albinism↗

Trichochromuria in melanosis of melanoma.

Two patients with metastasizing melanoma and diffuse melanosis have previously been reported to excrete large quantities of trichochromes in the urine. The present study describes 2 further melanoma patients with diffuse melanosis and trichochromuria. The hair of one of the patients which had been red in childhood and turned brown in adult age returned to red with the appearance of melanosis. Normal excretion of a methylated melanocytic metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid, was observed in this patient, possibly indicating exhaustion of the methylating system. The other patients excreted large quantities of 6-hydroxy-5-methoxyindole-2-carboxylic acid. Both patients showed highly increased excretion of 5-S-cysteinyldopa. Both patients with melanosis exhibited fine electrone-dense granules in lysosomes of dermal histiocytes. The findings support the concept that trichochromes or similar pigments in dermal histiocytes are responsible for diffuse melanosis in melanoma patients.

Adult↗

Metabolism of 5-S-glutathionyldopa.

5-S-Glutathionyldopa is oxidized at incubation with tyrosinase and dopa producing a black pigment. The reaction proceeds with the formation of two chromophores with absorption spectra similar to those of dopachrome and melanochrome, respectively. Zn2+ catalyses the formation of the melanochrome-like compound. The oxidation of 5-S-glutathionyldopa by dopaquinone, formed by the action of human tyrosinase and mushroom tyrosinase, is considerably slower than that of 5-S-cysteinyldopa. The higher oxidation potential of 5-S-glutathionyldopa, and/or the greater number of dopaquinone molecules necessary for pigment formation from 5-S-glutathionyldopa and/or the formation of tyrosinase-inhibiting products from 5-S-glutathionyldopa can explain the slower oxidation of this compound. The oxidative pathways suggested for 5-S-glutathionyldopa by the present findings may be relevant both in the melanocyte and in non-specific oxidation of cathechols occurring in other cells.

Basidiomycota↗

Detection of 5-S-cysteinyldopamine in human brain.

5-S-Cysteinyldopamine was synthesized and used as reference compound in HPLC analyses of extracts from various regions of human brain. The compound could be detected in brain regions rich in dopamine (caudate nucleus, putamen, globus pallidus and substantia nigra) but not in other regions (cerebellum, occipital cortex). The occurrence of 5-S-cysteinyldopamine in dopaminergic brain regions supports the hypothesis that dopamine in part undergoes autoxidation, leading to formation of highly reactive quinones. The newly discovered metabolite may prove useful in future studies of dopamine autoxidation and the possibly resultant cytotoxicity in aging and degenerative brain disorders.

Aged↗

Increased polyamine formation in rat salivary glands by stimulation of their autonomic nerve supply.

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, was measured in the three major salivary glands of rats and mice. Enzyme activity and glandular putrescine content increased after continuous stimulation of the parasympathetic or sympathetic salivary nerves for 3 h. The activity was markedly reduced in animals fasted for 24 h to decrease nervous-reflex activation of the glands. Thus ODC activity may be linked with synthesis of secretory macromolecules.

Animals↗

Brain monoamine metabolism and behavior in portacaval-shunted rats.

Animals with a portacaval shunt exhibit several biochemical abnormalities in plasma and brain similar to patients with portal-systemic encephalopathy, i.e., hyperammonemia, amino acid imbalance, and neurotransmitter disturbances. We investigated behavior and brain monoamine metabolism in operated, sham-operated, and nonoperated rats 1 day and 2, 4, and 6 weeks after operation. In order to quantitate the turnover in the brain indoleamine and catecholamine systems, 5-hydroxytryptophan (5-HTP) and dihydroxyphenylalanine were measured after decarboxylase inhibition with NSD 1015. The brains were dissected into five regions. All rats with the shunt had high plasma ammonia concentrations. Behavioral tests revealed a reduction in spontaneous locomotion 2, 4, and 6 weeks after portacaval shunt and reduced exploratory behavior compared with control rats. These changes coincided with profound alterations of the indoleaminergic system. As early as 1 day after surgery, rats with the shunt showed a marked increase in the accumulation of 5-HTP in all brain regions, indicating an enhanced tryptophan hydroxylase activity. The changes in indoleamine synthesis were most profound in the cortex and the midbrain. Only minor alterations of the catecholaminergic system could be detected. The alterations in behavior and indoleamine neurotransmitter metabolism may be pathophysiologically interrelated and may serve as the basis for experimental studies of portal-systemic encephalopathy.

Animals↗

Renal polyamine metabolism in rats with renovascular hypertension.

A standardized stenosis was induced by applying a silver clip around the left renal artery in male rats. This resulted in arterial hypertension within 10 days (as determined by increase in heart weight). Ornithine decarboxylase (ODC) activity was determined in the right (untouched) kidney, the left kidney, and the adrenal glands 1 day, 10 days, and 3 months after the operation. There was no difference in ODC activity in the right kidney of the operated animals when compared with matched controls. In the left kidney (with artery stenosis), ODC activity decreased to 40% after 1 day. A partial recovery was seen after 10 days (ODC activity 70% of normal), and after 3 months ODC activity had normalized. Removal of the clip 1 day prior to killing induced in the 3-month group a more than two-fold increase in ODC activity in the previously clipped kidney; ODC activity in the contralateral kidney was not affected. Only minor changes in ODC activity occurred in the adrenal glands following the operation. Contents of putrescine and spermidine were increased in the left (stenotic) kidney, and after clip removal, also in the right (untouched) kidney. Our observations thus indicate that alterations in renal blood flow are rapidly followed by changes in ODC activity. Contents of putrescine, spermidine and spermine seemed to a great extent to be independent of the ODC activity.

Adrenal Glands↗

Ornithine decarboxylase activity and polyamines in the anterior pituitary gland during the rat oestrous cycle.

The biosynthesis of polyamines, an ubiquitous group of amines shown to be essential for normal cellular growth and differentiation, was studied in the rat anterior pituitary gland during the different stages of the oestrous cycle. The activity of ornithine decarboxylase (ODC), which catalyses the rate-limiting step in the biosynthesis of polyamines, was low during oestrus, metoestrus and dioestrus. However, a marked transitory rise in ODC activity was found in the pituitary gland on the evening of pro-oestrus. The rise in ODC activity was accompanied by an increase in the pituitary content of the polyamines putrescine and spermidine. Ovariectomy did not significantly change the basal ODC activity in the pituitary gland. Oestrogen treatment of ovariectomized rats resulted in a marked stimulation of pituitary polyamine biosynthesis. The largest effects were observed when oestrogen was given as two injections 72 h apart, which gave rise to levels of ODC activity comparable to those observed on the evening of pro-oestrus. The increase in polyamine synthesis in the anterior pituitary gland during pro-oestrus appeared not to be related to the preovulatory secretion of LH or prolactin, since neither LH-releasing hormone nor thyrotrophin-releasing hormone (which induces a secretion of prolactin) affected pituitary ODC activity. The observed biosynthesis of polyamines may be associated with the cellular proliferation which occurs in the anterior pituitary gland at oestrus.

Animals↗

Effect of different denervation procedures on catecholamines in the gut.

Sympathectomy has been used to study the role of the sympathetic nervous system in the control of gastric acid secretion. Conflicting results may reflect differences in the sympathectomy procedures used. In a previous study we showed a reduction of catecholamines by more than 90% in the gut wall of the rat after surgical upper abdominal sympathectomy. The aim of the present investigation was to ascertain whether chemical sympathectomy was equally effective and whether total denervation, including combined chemical and surgical sympathectomy together with bilateral truncal vagotomy, would lower the catecholamine levels further. The results showed that chemical sympathectomy reduced noradrenaline levels in fundus (oxyntic) and antrum mucosa to levels similar to those after surgical sympathectomy (less than 5%), but the reduction was less pronounced in the muscle layer of the fundus and antrum and in the pancreas and spleen. Combined surgical and chemical sympathectomy did not reduce noradrenaline more effectively than surgical sympathectomy alone. Vagotomy reduced catecholamines in the stomach by about 50%; in extragastric tissues vagotomy was without effect. Total denervation, including combined surgical and chemical sympathectomy plus vagotomy, did not reduce noradrenaline levels more than surgical sympathectomy alone, suggesting that the proportion of adrenergic fibers that derive from the vagus is quantitatively insignificant but that the vagus exerts a local control of the sympathetic stores of gastric catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Production of 6-hydroxydopa by human tyrosinase.

A tyrosinase obtained from cultured human melanoma cells was found to oxygenate 2,4-dihydroxyphenylalanine to the strongly cytotoxic amino acid 6-hydroxydopa (2,4,5-trihydroxyphenylalanine). The oxygenation was dependent on the presence of a reducing co-substrate such as dopa or dopamine. The rate of oxygenation of 2,4-dihydroxyphenyl-D,L-alanine was similar to that of L-tyrosine, the normal substrate of tyrosinase. The enzymatic reaction demonstrated may prove of value in the chemotherapy of human melanoma.

Catalysis↗

Melanocyte metabolites in the urine of people of different skin colour.

The urinary excretion of 2 melanocyte metabolites was studied in normal people of different skin type. The sulphur-free indole derivative 6-hydroxy-5-methoxyindole-2-carboxylic acid was excreted in larger quantities by people with genetically dark skin, whereas the excretion of 5-S-cysteinyldopa was not related to pigment type. No correlation between 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid excretion emerged.

Adult↗

Oxidation of dopa in human albinism.

The urine of an albino woman contained small quantities of 5-S-cysteinyldopa; 6-hydroxy-5-methoxyindole-2-carboxylic acid, a melanin precursor metabolite, was lacking. The 5-S-cysteinyldopa excretion observed may reflect non-specific oxidation of dopa. Two other albino patients showed normal values for the excretion of 5-S-cysteinyldopa and of 6-hydroxy-5-methoxyindole-2-carboxylic acid.

Adult↗

Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid: differences between pigmented and albino mice.

Urinary excretion of the phaeomelanin precursor 5-S-cysteinyldopa (5-S-CD) and the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI-2-C) was studied in black and albino mice. The urinary concentration of 5-S-CD was 31.7 ng/ml in black and 16.1 ng/ml in albino mice. The concentration of 6H5MI-2-C was 21.0 ng/ml in the urine of black mice. The compound could not be demonstrated in the urine of albino mice.

Albinism↗