PubMed Health⌕ Search

Biomedical subjects

V Lucini

Publications and source records attributed to V Lucini.

50 records · Page 3Linked to original sources
PubMed1992

Melatonin signal transduction and mechanism of action in the central nervous system: using the rabbit cortex as a model.

The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particularly abundant is the parietal cortex. Consequently, we characterized the putative melatonin receptor in the parietal cortex by a series of in vitro ligand-receptor binding experiments and biochemical and electrophysiological studies. The in vitro saturation and competition experiments demonstrated that the binding in the crude cortical membrane preparations was of high affinity and specificity. Guanine nucleotides (GDP, GTP, and GTP gamma S) inhibited the specific 2-[125I]iodomelatonin binding in a dose-dependent manner. Coincubation with a nonhydrolyzable GTP analog provoked a shift in the binding affinity; the numerical values of the Kd increased from 20-30 to 200-600 pM. Melatonin, in nanomolar concentrations, was able to inhibit the forskolin-stimulated accumulation of cAMP in parietal cortex explants, and preincubation with pertussis toxin counteracted this effect of melatonin. Apparently, the melatonin binding site in the rabbit parietal cortex is linked to its second messenger via a pertussis toxin-sensitive G-protein, probably of the inhibitory Gi class, similar to what has been described for different parts of the brain of other vertebrates. The experiments on the spontaneous firing activity of single neurons in the third to fourth layer of the parietal cortex in anesthetized animals showed that melatonin and its potent agonist 2-iodomelatonin exhibited gamma-aminobutyric acid (GABA)-like effects and were able alone, in nanomolar concentrations, to significantly slow the neuronal firing activity. Moreover, both melatonin and 2-iodomelatonin potentiated the effect of GABA on the neuronal activity, leading to powerful inhibition of the tested neurons. Undoubtedly, the binding site in the rabbit parietal cortex possesses all of the characteristics of a functional receptor. We suggest that melatonin is involved in the control of fundamental cortical functions and that it acts in concert with GABA, one of the two major inhibitory neurotransmitters in the central nervous system.

Animals↗
PubMed1991

Localization and characterization of melatonin binding sites in the brain of the rabbit (Oryctolagus cuniculus) by autoradiography and in vitro ligand-receptor binding.

The distribution and the properties of the melatonin binding sites were characterized in the brain of the rabbit by combined use of autoradiography and in vitro ligand-receptor binding. Autoradiography revealed widespread specific binding in the brain. The pars tuberalis of the pituitary gland, suprachiasmatic nuclei, ventromedial hypothalamic nuclei, tapetum, hippocampus, indusium griseum, cingulate gyrus, cortex and the choroid plexus were intensely labelled. Diffuse specific binding was recorded in the olfactory bulb and the anterior hypothalamus. Series of in vitro ligand-receptor binding experiments, using the anterior hypothalamus, confirmed that the binding was of high affinity and specificity. Coincubation with a non-hydrolyzable GTP analogue provoked a shift in the binding affinity, the numerical values of the Kd increasing from 20-30 pM to 280-300 pM. Apparently the melatonin receptor in the rabbit brain is linked to its second messenger via a G protein, similarly to what has been described for the brain of other vertebrates.

Animals↗
PubMed1991

In vivo and in vitro studies on modulation of the pineal endocrine function by L-acetyl-carnitine in the rat.

Male Sprague-Dawley rats injected (i.p.) at 1500h with L-acetyl-carnitine in doses of 10, 30 or 90 mg/kg exhibited a notable increase in their pineal and serum melatonin content 1 hr later. Likewise, L-acetyl-carnitine administered in the same dose range induced a significant increase of pineal and serum melatonin content in rats treated at 0100h, following exposure of 30 min to bright white light to suppress endogenous melatonin. Under in vitro experimental conditions, however, 60 min of coincubation of isolated rat pineal glands with L-acetyl-carnitine (10(-5) M) did not result in an elevation in melatonin accumulated in the incubation medium. These results demonstrate that, in vivo, L-acetyl-carnitine can exert a modulatory action on synthesis and release of melatonin, possibly by modifying noradrenergic transmission and signal transduction in the pineal gland.

Acetylcarnitine↗
PubMed1991

Characterization and mapping of melatonin receptors in the brain of three mammalian species: rabbit, horse and sheep. A comparative in vitro binding study.

Melatonin receptors were characterized in the brains of three mammals (rabbit, horse and sheep) by an in vitro binding technique, using 2-[125I]iodomelatonin as labelled ligand. Although binding sites for melatonin have been described recently in several vertebrate species (including the sheep), the rabbit and the horse have not been the subject of investigation so far. Apart from characterization, the present report describes receptor distribution in a number of brain regions, thus allowing for direct interspecies comparison under the same methodological conditions. 2-[125I]iodomelatonin labelled high-affinity binding sites in crude membrane preparations from these species. A series of kinetic and saturation experiments revealed that the binding was rapid, stable, saturable, reversible, of high affinity (Kd in the low picomolar range) and low capacity (Bmax between 1 and 20 fmol/mg protein). The competition studies showed that the relative order of potency of a variety of indoles for inhibition of 2-[125I]iodomelatonin binding was as follows: 2-iodomelatonin greater than 6-chloromelatonin greater than melatonin much much greater than 5-methoxytryptophol greater than 5-methoxytryptamine, and that it was similar in the different brain regions. Prazosin, which has been reported as an extremely potent melatonin analog in the hamster brain, possessed no potency in all preparations from different regions in the three species under investigation. The regional distribution of the receptor showed insignificant species differences. Highest density was always recorded in the median eminence/pars tuberalis (ME/PT) area. Other regions (SCN, POA and certain cortical areas), showed lower, but significant, receptor content. Saturation and competition studies revealed that these binding sites were also of high affinity, low capacity and high specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Alpha-1 adrenoceptor involvement in the control of melatonin secretion in the golden hamster.

The nocturnal peak in pineal and serum melatonin content was reduced following administration of the selective alpha-1 adrenoceptor antagonist prazosin in a dose of 0.25 mg/kg. The effect was pronounced one hour post treatment during the late dark phase of the daily photocycle. These data confirm the reported findings that the hamster pineal sensitivity to adrenergic challenge is confined to the second part of the dark phase and indicate that postsynaptically located alpha-1 adrenoceptors are also involved in the physiological control of melatonin synthesis and/or release in that species.

Animals↗
PubMed1990

Failure of prazosin to mimic the effects of melatonin under in vivo and in vitro conditions.

The gonads of male hamsters exposed to short photoperiod (LD, 10:14) or treated with melatonin in the late afternoon under long photoperiod (LD, 14:10) had undergone complete regression by the end of the treatments (8 weeks). Animals treated for the same period of time with prazosin (a putative melatonin analogue) under the same conditions failed to show a difference in their gonadal status as compared to the long photoperiod controls. Prazosin was unable to prevent melatonin-induced gonadal atrophy when injected either in the morning or 30 min before melatonin. Moreover, prazosin was without any effect on (and unable to prevent the melatonin-stimulated) progesterone production by rat adrenals under in vitro conditions. These data demonstrate that prazosin, which reportedly inhibits 2-[125I]iodomelatonin binding in the hamster brain in an affinity-related manner, does not possess properties of a biological melatonin analogue under conditions of two different model systems in two species.

Adrenal Glands↗
PubMed1990

Comparison of the rat pinealocyte ultrastructure with melatonin concentrations during daytime and at night.

The aim of this study was to investigate the ultrastructure of rat pinealocyte during daytime (1600 h) and at night (0100 h) and to compare these observations with serum melatonin levels in the same animals. In addition, pineal melatonin concentrations were determined in other animals. Both serum and pineal melatonin concentrations were significantly higher at night than during daytime (34 and 21 times, respectively). Sizes of pinealocytes, their nuclei, and nucleoli, as well as cross-sectional areas of mitochondria and granular endoplasmic reticulum were also higher at night than during daytime, whereas areas of lysosomes, Golgi apparatus, and vacuoles containing flocculent material did not differ at the time points studied. In contrast, the number of dense-core vesicles was higher during daytime. The results of the present study show that morphological patterns of higher metabolic activity of the rat pinealocyte at night when compared to those during daytime correlate with melatonin concentrations.

Animals↗
PubMed1989

Cytosolic androgen receptors in the neuroendocrine tissues of the golden hamster: influence of photoperiod and melatonin treatment.

Hamsters exposed for eight weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod (LD 14:10) had significantly higher number of cytosolic androgen receptors in the pituitaries, hypothalami and harderian glands, as compared to the long photoperiod (LD 14:10) exposed controls. The numerical value of the apparent Kd was two to three times lower in the hypothalami and pituitaries, but not in the harderian glands of the animals from these groups. These results indicate that alterations in receptor numbers and affinity constants may be responsible for the dramatic changes in the sensitivity of the hypothalamo-pituitary axis to the negative feedback actions of the gonadal steroids, observed under inhibitory photoperiods and that this effect could be duplicated by late afternoon melatonin treatment.

Animals↗
PubMed1988

Relation between lymphocyte subpopulations and pineal function in patients with early or metastatic cancer.

It has been demonstrated that melatonin and other pineal hormones play a role in the neuroendocrine control of immunity. Anomalies of both pineal and immune functions have been reported in cancer. Pineal and lymphocyte functions, however, have never been simultaneously evaluated in oncologic patients. This preliminary study was carried out in order to analyze the melatonin-lymphocyte relationship in human neoplasms. In a first investigation, we evaluated melatonin serum levels and lymphocyte subpopulations on venous blood samples collected during the morning from 46 healthy controls and from 27 cancer patients, 13 of whom had metastases, while the other 14 were without metastases. Moreover, melatonin levels were high in 10 oncological patients and within the normal range in the other 17 cases. B lymphocyte (B), total T lymphocyte (T3), T helper/inducer (T4) and T suppressor/cytotoxic (T8) mean percentages and T4/T8 mean ratios did not significantly differ, either between patients with high and normal melatonin levels, or between metastatic and nonmetastatic cancer patients. In a second study, we evaluated the effects of a prolonged treatment with melatonin (20 mg/daily intramuscularly at 3:00 p.m. for 2 months) on 8 patients with advanced cancer, in whom conventional antitumor therapies had failed. Mean percentages of B, T3, T4, T8 lymphocytes and T4/T8 mean ratios were not significantly different before or after melatonin treatment. In only one patient did the T4/T8 ratio decrease after therapy; in this case only, a stabilization of the disease was obtained, while in all 7 other patients the neoplastic disease progressed also during melatonin treatment, even if an evident improvement of the performance status was seen as it was in most cases. These results seem to exclude that melatonin may influence lymphocyte functions in cancer. Longitudinal studies and further data, however, will be needed to clarify this question.

Adult↗
PubMed1987

Clinical study of melatonin in untreatable advanced cancer patients.

It is known that the pineal gland has some antitumor activity. Melatonin, its most important hormone, has been shown to inhibit tumor growth in vivo and in vitro. Moreover, some investigations have demonstrated an altered melatonin secretion in cancer patients. Despite these interesting data, clinical trials have never been carried out to evaluate the effects of melatonin on human neoplasms. The aim of this study was to draw some preliminary conclusions on melatonin therapy in advanced human neoplasms. Nineteen patients suffering from advanced solid tumors, which did not respond to standard therapies, entered the study. Performance status (PS) was 20 or less in 9 cases, and more than 20 in the other 10. Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period with lower doses in patients who had a remission, a stabilization of disease or an improvement in PS. Among patients with a PS higher than 20, a partial response was achieved in one case with cancer of the pancreas; moreover, 5 of 10 had stable disease, but the other 4 cases had a progression; an evident improvement of PS was obtained in 6 of the 10 cases. In contrast, among patients with a very poor PS, 7 of 9 died within the first 2 months of therapy. This preliminary study would suggest that melatonin may be of some value in treating cancer patients in whom standard antitumor therapies have failed, particularly in improving their PS and quality of life.

Adult↗
PubMed1985

Effect of progesterone on the sexual behavior of the male Japanese quail.

The reduced metabolites of testosterone produced in the central nervous system of birds are known to be involved in the regulation of male sexual behavior. Since progesterone may compete with testosterone for 5 alpha- and 5 beta-reduction, it may also interfere with the sexual behavior of birds. In order to test this hypothesis, progesterone was administered to male quail either transferred from short days to long days or kept in short days and treated with testosterone. Sexual behavior and crowing were scored at intervals for 21 days and the size of the cloacal gland was measured at the same times. On Day 21, the birds were killed and their testes were weighed. The administration of a large dose (1 mg/day) of progesterone depressed the sexual behavior of the birds stimulated either by long days or by the administration of testosterone. It is suggested that progesterone may compete with testosterone for the active sites of 5 alpha- and 5 beta-reductase; alternatively, its effect may be due to an antiandrogenic activity.

Animals↗
PubMed1984

Brain testosterone metabolism in thyroidectomized and thyroxine-treated chickens.

The metabolism of testosterone to reduced derivatives was studied in the pituitary gland, the hypothalamus, and the hyperstriatum dorsale of thyroidectomized, sham-operated, and thyroxine (T4)-injected immature cockerels. The levels of plasma thyroid hormones were markedly reduced (P less than 0.001) in thyroidectomized cockerels whereas thyroidectomized or sham-operated birds injected daily with 100 micrograms/kg thyroxine had significantly elevated (P less than 0.001) levels in comparison with sham-operated control birds. Each tissue was found to produce significant amounts of 5 beta-androstane-17 beta-ol-3-one (5 beta-DHT), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta-3 alpha-diol), and androstenedione. Irrespective of thyroid state 5 beta-DHT and 5 beta-3 alpha-diol were produced to the greatest extent by the hyperstriatum dorsale whereas androstenedione was maximally produced in the pituitary gland. In comparison with the hyperstriatum dorsale and the hypothalamus only small quantities of 5 beta-DHT were produced in the pituitary gland. In the hyperstriatum dorsale of thyroidectomized birds both 5 beta-DHT (P less than 0.05) and 5 beta-3 alpha-diol (P less than 0.1) were formed to a greater extent than in sham-operated birds. This effect was reversed by administration of T4 to the operated birds which reduced the levels to those measured in the sham-operated controls. Similarly, injection of T4 into sham-operated birds decreased (P less than 0.05) the production of 5 beta-DHT in the hypothalamus while in the pituitary gland injection of T4 into thyroidectomized birds reduced the production of androstenedione (P less than 0.05). It was concluded that in the cockerel thyroid hormone is likely to play a role in the metabolism of testosterone. The physiological significance of 5 beta-reductase activity in the neuroendocrine tissues is discussed.

Androstane-3,17-diol↗
PubMed1983

Effect of photoperiod and gonadectomy on testosterone metabolism in vitro by the prostate of the golden hamster.

Testosterone metabolism was studied in vitro in the prostate of intact and castrated golden hamsters maintained either in short days (8 h light: 16 h darkness, 8L: 16D) or in long days (14L: 10D). Testosterone was found to be converted into 17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-DHT), 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3, 17-dione and androstenedione. The mean conversion of testosterone to 5 alpha-DHT was higher in prostates from animals maintained in long days than in short days (P less than 0.0025) while that to androstenedione was higher in short days (P less than 0.0005); no significant changes in the formation of the other three metabolites were noted. Castration of animals maintained in short days resulted in a significant (P less than 0.05) decrease in the mean conversion to all four metabolites. In contrast, castration of animals kept in a long-day regime caused a significant (P less than 0.01) decrease in the mean formation of 5 alpha-DHT but a significant (P less than 0.05) increase in the mean formation of 5 alpha-androstane-3 alpha, 17 beta-diol.

Androstane-3,17-diol↗