Biomedical subjects

I Ebels

Publications and source records attributed to I Ebels.

At least 37 records · Page 2Linked to original sources

PubMed1985

The effect of reduced neopterin on the synthesis of several methylated indoles in the pineal gland of adult male golden hamsters, kept under standardized conditions.

In the present study the effect was tested of reduced neopterin (RN) on the methylating capacity of the pineal gland of adult, male golden hamsters, housed under standardized conditions throughout the year. An effect of RN on the synthesis of a number of methylated compounds was, indeed, demonstrated. It is concluded that RN not only influences the indole metabolism by being the cofactor of tryptophan-hydroxylase, but that it might be involved in the regulation of other enzymes as well. Incubation with RN was most effective at the end of the light period. As this is also the time at which melatonin (aMT) injections cause gonadal atrophy in hamsters, kept under long photoperiod, this time of the day may be very important for aMT synthesis. A season-bound influence of RN was also demonstrated. The effect of RN was stimulatory in September, November and January for 5-methoxy-tryptamine (MT) and in November for 5-methoxytryptophan (MW) synthesis, but inhibitory in July. Furthermore, the effect of RN was stimulating for 5-methoxyindole-3-acetic acid (MA) and aMT in September, while the influence in the other months tested was absent or slightly inhibiting. These results suggest that the influence of RN in the pineal may be regulatory to various enzymes of the indole metabolism.

5-Hydroxytryptophan↗

PubMed1985

The effect of ovine pineal compounds prepared under red or green light on the activity of male rat anterior pituitaries in vitro.

A high molecular weight fraction XM100R (MW A 100,000) was prepared by ultrafiltration from ovine pineals using two different extraction methods under red light conditions (lambda greater than 600 nm). This fraction stimulates the release of radioimmunologically active luteinizing hormone (LH) of anterior pituitaries in vitro. The ultrafiltration fraction PM30R (MW greater than 30,000 and less than 100,000) was found to be radioimmunologically active only when the "Bensinger" extraction procedure was applied. However, when comparable fractions were prepared under green light and incubated with half-pituitaries, all the incubation media of the ultrafiltrated fractions, XM100R, PM30R, PM10R (MW greater than 10,000 and less than 30,000) UM2R (MW greater than 1000 and less than 10,000), UM05R (MW greater than 500 and less than 1000) and UM05F (MW greater than 500), reacted with anti-LH. This may mean that under green light conditions the high molecular weight ovine pineal compounds in XM100R are disintegrated and/or split up into small molecules which can stimulate the release of LH, or crossreact with the anti-LH serum.

Animals↗

PubMed1984

Lethal mutations induced in Drosophila melanogaster by direct or indirect action of pteridines.

The experiments described in this paper show that synthetic pteridines, especially biopterin and pterin, injected directly into Drosophila melanogaster induce recessive lethals. On the contrary, D-neopterin seems to have little effect. A mutagenic effect has previously been shown for an extract of Pieris brassicae in diapause, treated with these pteridines and tetrahydrofolic acid (FH4). It appears that chromosome II is more sensitive to these mutagenic treatments than chromosome X.

Animals↗

PubMed1983

Influence of some pteridines on pineal 5-methoxyindole synthesis in male Wistar rats periodically exposed to either white or red light.

In previous investigations the change of circadian rhythmicity in pineal melatonin/5-methoxytryptophol synthesis of rats periodically exposed to red light was similar to that in pineals of rats incubated with pterin-6-aldehyde. These experiments were, however, performed with rats of different age and in different periods of the year. In the present study these two factors influencing pineal indole metabolism have been combined the experiments being carried out in rats aged 28 days and during the same day in the month of January. It was observed that under influence of red light the peak of melatonin/5-methoxytryptophol synthesis shifted towards daytime, whereas incubation with pterin-6-aldehyde did not cause such a shift. If under different experimental conditions the mean amount of melatonin/5-methoxytryptophol which was formed over a 24 hour period was compared, it appeared that pineals of rats exposed to white light incubated with reduced neopterin but not pineals incubated with pterin-6-aldehyde behave in this respect similar to pineals of rats exposed to red light. However, if the ratio between melatonin/5-methoxytryptophol and 5-methoxytryptamine is calculated pineals of white light exposed rats incubated in pterin-6-aldehyde behaved very similar to the pineals of rats exposed to red light. Although the role of pteridines remains obscure, it appears that the parameters 2. circadian rhythmicity and 2. the amount of 5-methoxyindoles and 3. the ratio between these indole derivatives might be of importance in analyzing their physiological effects. The influence of application of light of different wavelengths and year rhythmicity is discussed.

Animals↗

PubMed1983

Effects of retinal and pineal low molecular weight fractions and antipsychotic drugs on hydroxyindole-O-methyltransferase.

Fractions from bovine retinas and sheep pineals of low molecular weight decrease the activity of purified hydroxyindole-O-methyltransferase (HIOMT). The antipsychotic drugs chlorpromazine and haloperidol show a similar effect under the same experimental conditions. It is suggested that they may imitate the effect of (an) unknown natural suppressor(s) of HIOMT-activity, present in retina and pineal, decreasing the biosynthesis of methoxyindoles.

Acetylserotonin O-Methyltransferase↗

PubMed1983

The influence of some pteridines on pineal 5-methoxyindole synthesis in male Wistar rats periodically exposed to either white or green light.

The pineals of 28 days old male Wistar rats, in December periodically exposed to either white or green light, were incubated with pterin-6-aldehyde or reduced neopterin. In white light the rhythm of synthesis of 5-methoxytryptophan and of 5-methoxyindole-3-acetic acid was clearly influenced by the pteridines mentioned. In green light a change in rhythmicity of 5-methoxytryptophan, 5-methoxytryptamine and of melatonin/5-methoxytryptophol synthesis by the pteridines was observed. In white light both pteridines increased 5-methoxytryptophan and decreased 5-methoxyindole-3-acetic acid synthesis. Reduced neopterin stimulated 5-methoxytryptamine synthesis and inhibited melatonin/5-methoxytryptophol synthesis. Pterin-6-aldehyde showed an opposite effect. In green light both pteridines decreased 5-methoxytryptophan synthesis, but increased 5-methoxyindole-3-acetic acid and 5-methoxytryptamine synthesis. Melatonin/5-methoxytryptophol synthesis was decreased by reduced neopterin and increased by pterin-6-aldehyde. The results suggest an indolic metabolic pathway leading from 5-methoxytryptophan via 5-methoxytryptamine to melatonin, while pteridines and light of different wave lengths are correlated in regulating indole metabolism.

5-Methoxytryptamine↗

PubMed1982

Inhibition of avian and mammalian hydroxy-indole-o-methyl-transferase (HIOMT) with low molecular weight fractions of mammalian pineal glands.

Partially purified fractions from sheep pineal gland extracts, which show a fluorescence like pteridines, were shown to suppress the enzyme hydroxy-indole-o-methyltransferase (HIOMT) isolated from avian pineals and retinas. The results described demonstrate that the mechanism of inhibition of HIOMT activity is independent of the species and organ. A blocking effect was found in experiments whether retinal or pineal HIOMT were used and the effect was found as well with bovine HIOMT. It is shown that low molecular weight molecules show inhibitory activity and accompany the high molecular weight enzyme HIOMT.

Acetylserotonin O-Methyltransferase↗

PubMed1982

Comparison of some peptidic and proteic ovine pineal fractions with a bovine pineal E5 fraction.

Using rather simple and mild extraction and separation methods, three ovine pineal fractions (XM 300 R-PP7.2' and PP7.2 S) were obtained, which contain peptidic/proteic substances and which show fluorescence characteristics of indoles. The ovine fractions were compared with the bovine pineal E-5 fraction. The ovine fractions are chemically sensitive to normal laboratory light and stable in red light (lambda greater than 600 nm). Immunologically, these fractions and the bovine E 5 fraction are stable. From the results of radioimmunological experiments it was concluded that the bovine pineal E 5 fraction as well as the ovine pineal fraction XM 300 R-PP7.2 and PP7.2S may contain (a) peptide(s) ending by the same carboxy terminal tripeptide Pro-Arg-Gly(NH2).

Animals↗

PubMed1982

Changes in the circadian rhythmicity of hydroxyindole-O-methyl transferase (HIOMT) activity in the synthesis of 5-methoxyindoles in the pineal gland of 28 day old male Wistar rats exposed to white, red and green light.

Hydroxyindole-O-methyl transferase activity for the synthesis of 5-methoxyindoles was investigated in the pineal gland of 28 day old male Wistar rats after exposure to white, red and green light for 12 hours daily. It could be demonstrated that, in comparison to white light, red light causes a shift of HIOMT activity for the synthesis of melatonin/5-methoxytryptophol towards an earlier period being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-method being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-method being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-methoxytryptophol to a later period, showing a peak at 24 hours. The synthesis of 5-methoxytryptamine is significantly increased at 24 hours. An increase is also observed in the synthesis of 5-methoxyindole-3-acetic acid at 12 and at 4 hours, times at which this synthesis is also maximal using white light, whereas the synthesis of 5-methoxytryptophan is generally decreased. A possible relationship between the present results and those obtained after exposure to different wavelengths of light on N-acetyltransferase activity, the effect of pterins on HIOMT activity and the effect of different wavelengths on gonadal growth are discussed.

5-Methoxytryptamine↗

PubMed1981

The role of the pineal gland in neuroendocrine control mechanisms of neoplastic growth.

A survey of papers read during a workshop held in Vienna, 1977, is given showing that the pineal gland can be considered a model for research on neuroendocrine control mechanisms in neoplastic growth. From data obtained by different authors it can be concluded that the role of the pineal indole melatonin is very important in regard of the incidence and the development of tumours. On the basis of all the facts mentioned in this paper it is obvious that pineal gland activity should be included into the neuroendocrine factors studied in relation with oncogenic processes. For future research a number of experimental approaches, which need special emphasis, are recommended.

Animals↗

PubMed1980

Presence of AVT-, alpha-MSH-, LHRH- and somatostatin-like compounds in the rat pineal gland and their relationship with the UMO5R pineal fraction. An immunocytochemical study.

Using antibodies against AVT, alpha-MSH, LHRH and somatostatin, immunoreactive cells were detected in the rat pineal gland. All of these antibodies stain the same cells, which also react immunocytochemically when an antibody against the UMO5R sheep pineal fraction, a fraction that presents antigonadotropic properties in vivo, is used. Relatively more immunoreactive cells are present in the pineals of young rats than in the pineals of adult animals. Comparison of the results obtained with different potent antibodies against each of the peptides, and a study of the staining properties of the antibodies in the pineal after solid phase absorption to different peptides or to different sheep pineal fractions, led to the proposal that the immunoreactivity found in the rat pineal is not due to the presence of AVT, alpha-MSH, LHRH or somatostatin, but to a cross-reaction of each of these antibodies with (an) unidentified compound(s). This compound is synthetized in the pineal gland, as was demonstrated using cultured pineals. The UMO5R and the Prot. 4 fractions of the sheep pineal seem to be chemically related to this unknown compound, the possible endocrine nature of which is discussed.

Aging↗

PubMed1980

A survey of the location, isolation and identification of indoles, pteridines and some unknown active substances in sheep pineals. The possible significance of pteridines for the neuroendocrine control of neoplastic growth.

Several indoles with mass spectra identical to those of synthetic melatonin, 5-hydroxyindole-3-acetic acid (5-HIAA), 5-methoxyindole-3-acetic acid (5-MIAA), 5-hydroxytryptophol (5-HTL) and 5-methoxytryptophol (5-MTL) could be located, isolated and identified in sheep pineal extracts using rather simple and mild extraction and separation methods. An antigonadotropin, which differs from melatonin, was isolated and partially purified from sheep pineals, using compensatory ovarian hypertrophy after unilateral ovariectomy as a bioassay. Antigonadotropic and gonadotropic compounds which differ from the indoles above mentioned could be located with the same methods. In vitro, these fractions act either on the hypothalamus or on the anterior pituitary. From the paper chromatography fraction, acting on the anterior pituitary in vitro, a compound could be isolated which is most probably identical with biopterin. In our opinion, however, this compound is not responsible for the antigonadotropic activity of the fraction, observed in vitro. Some pineal fractions showing an effect on the activity of the hypothalamus or anterior pituitary of male rats and mice in vitro, may be also active in some experimental tumour models. A possible relationship between disorders in pteridine metabolism and neoplastic growth is discussed.

Animals↗

PubMed1980

Biosynthesis of taurine by rat pineals in vitro.

Pineal glands from adult, male rats were incubated in oxygenated Krebs-Ringer buffer containing 14C-cystine. After three hours the incubation media and pineal gland extracts were placed separately on Dowex AG W50-X-4 columns. In the elution volume where 14C-labeled taurine is found a labeled peak was recovered. However, when subjected to one or two dimensional paper chromatography especially the eluants from pineal gland extracts yielded two 14C-labeled substances one located in the region where unlabeled taurine is detected by ortho-phthalaldehyde reagent. These results were confirmed utilizing a method developed in our laboratory based on high performance liquid chromatography (HPLC). The pineals, as well as their respective incubation medium, were shown to contain radioactive taurine. These results demonstrate that rat pineal glands are capable of taurine synthesis. Also a high degree of labeling was associated with an area on paper chromatograms, migrating more rapidly than the standards, using acidic solvent systems. If represented by a single pineal compound, the substance must be rapidly synthesized from 14C-cystine to account for the radioactivity observed. Future studies of sulfur metabolism within the pineal gland could be of significant interest.

Animals↗

PubMed1980

The influence of some pterins on the circadian rhythmicity of hydroxyindole-O-methyl transferase in the pineal gland of 42-day old male Wistar rats.

The influence of three pterin derivatives on the diurnal fluctuations of HIOMT (hydroxyindole-O-methyl transferase) activity was studied in the isolated pineal glands of 42-day old male Wistar rats during the month of October. The method used permitted the separate determination of four HIOMT activities. --Reduced neopterin stimulated the methylation of the substances, 5-HTP, 5-HT and 5-HIAA (see abbreviations in Material and methods), during the night. HIOMT action on the combinations N-Ac-5-HT/5-HTL was shifted to a later moment in the dark period. --Pterin-6-aldehyde stimulated HIOMT action on 5-HT during the daytime. HIOMT action on the substrates 5-HTP, 5-HIAA and N-Ac-5-HT/5-HTL was shifted towards an earlier period. --Isoxanthopterin did not exert any influence on diurnal variation in the four HIOMT activities. It may be concluded that reduced neopterin and pterin-6-aldehyde influenced the activity and the circadian rhythmicity of 5-methoxyindole synthesis. Those alterations might be important in the regulation of reproduction.

5-Hydroxytryptophan↗

PubMed1980

Pteridines as nonretinal regulators of light-dependent melatonin biosynthesis.

6-Formylpterin was purified by paper chromatography, and bovine pineal hydroxyindole-O-methyltransferase (S-adenosyl-L-methionine:N-acetylserotonin O-methyl-transferase; EC 2.1.1.4) was purified by flat-bed gel electrofocusing. Fractions of the methyltransferase with isoelectric points at pH 5.0, 5.7, and 5.2 were tested in the presence of 6-formylpterin, and decreased activities were found. Because 6-formylpterin is one of the photolytic products of folic acid and decreased serum folic acid has been reported in light-exposed men, we suggest that pteridines may be involved in nonretinal effects of light on pineal melatonin biosynthesis. It may be that this metabolic pathway is an evolutionary relic of primitive light responses of pigmentation mechanism.

Acetylserotonin O-Methyltransferase↗

PubMed1980

Extraction of pineal and uterine tissue at different pH values: a preliminary report on the occurrence of a few groups of compounds in both tissues.

Extraction of pineal glands has been performed at different pH values. After extraction at pH +/- 4.9, 'porphyrin'-containing protein did not occur in the extracts, while at pH +/- 6.3 these proteins had passed over partly into the extract; at pH +/- 6.8 the proteins could no longer be detected in the residues, but a partial breakdown had taken place. The activity of pineal extracts depends on the method of extraction. In the watery extracts (pH +/- 6.3) both of pineal and of uterine tissue the presence could be shown among others of: porphyrins bound to protein, the indole compound 'bufotenine' also bound to protein, 'kynurenine', a 'basic peptide' containing amines and 'flavoproteins'. The hypothesis is proposed that in uterine endometrium, tryptophan can be metabolized in at least two pathways, one leading to kynurenine and one to bufotenine. Formation of bufotenine, probably a physiologically important compound, might be influenced by the oestrous cycle and conversely.

Animals↗

PubMed1979

Effects of sheep pineal fractions on the activity of male rat hypothalami in vitro.

High molecular weight substances could be isolated from sheep pineals with the "Bensinger" extraction method, followed by ultrafiltration of the waterlayer through different diaflomembranes. Two of the pineal fractions, XM100R and PM30R, stimulate the gonadotropin releasing activity of the medial basal hypothalamus (MBH). In experiments in which comparable pineal fractions were incubated without MBH and without pituitary and injected in immature mice no effect was detectable. All experiments in which a similar amount of rat cerebral cortex was used for incubation with pineal fractions did not show any activity.

Animals↗

PubMed1979

Location by paper chromatography of compensatory ovarian hypertrophy (COH) inhibiting activity in isobutanol extracts of bovine pineals.

Bovine pineal glands were extracted according to the methods reported by Bensinger et al. (1973) and Cheesman and Fariss (1970). Isobutanol soluble COH-inhibiting activity was further separated by chromatography on Sephadex G-15 and paper chromatography. With the Bensinger method, different active pineal fractions were obtained from Sephadex G-15 columns. Certain of those fractions were further separated by paper chromatography in butanol : acetic acid : water (4 : 1 : 1) and the COH-inhibitor was localized. The pineal COH-inhibitor could also be localized by high pressure, reverse phase liquid chromatography. More COH-inhibiting activity was extracted with the Bensinger method than with aqueous and acetic acid extraction methods used earlier by us. The Cheesman extraction method for arginine vasotocin gave less regular results in our hands than the Bensinger extraction method.

Animals↗