bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analgesic effects on endogenous melatonin secretion
Authors: Lapwood Keith R. , Bhagat Lakshmi , Simpson Mark P. 
Published: February 2007

Lapwood KR, Bhagat L, Simpson MP. Analgesic effects on endogenous melatonin secretion. J. Pineal Res. 1997; 22:20–25. © Munksgaard, CopenhagenAbstractAnimal welfare concerns have led to increased demands for use of postoperative analgesia in association with experimental surgery. Such treatment is appropriate provided it has no effect on experimental parameters. In order to assess any effects of analgesics on endogenous melatonin production, groups of six ewes were bled at 30 min intervals for the first 4 hr of darkness a) without analgesic treatment and b) immediately after analgesic administration. Analgesics tested were ketoprofen, phenylbutazone (both non‐steroidal anti‐inflammatory drugs or NSAIDs) and buprenorphine (an opioid). Plasma melatonin was measured by radioimmunoassay and 4 hr secretion profiles computed for each animal. Ketoprofen and buprenorphine treatment reduced mean four hour melatonin secretion profiles by 50.6% (from 1,347.3 to 665.1 pg/ml‐hr) and 38.6% (from 287.8 to 171.3 pg/ml‐hr), respectively. Only in the case of phenylbutazone was the response not statistically significant; hence this drug has been selected as a post‐operative analgesic for future experimental studies involving measurement of melatonin levels.
Nocturnal changes in pineal melatonin synthesis during puberty: Relation to estrogen and progesterone levels in female rats
Authors: Okatani Yuji , Watanabe Kazushi , Morioka Nobuyuki , Hayashi Kazutoshi , Sagara Yusuke 
Published: February 2007

Okatani Y, Watanabe K, Morioka N, Hayashi K, Sagara Y. Nocturnal changes in pineal melatonin synthesis during puberty: Relation to estrogen and progesterone levels in female rats. J. Pineal Res. 1997; 22:33—41. © Munksgaard, CopenhagenAbstractOur objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5‐hydroxytryptamine (5‐HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid‐dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5‐HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5‐HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol‐17β capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 |μg, 20 μg) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5‐HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 μg)produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 μg/day) for 2 weeks did not produce any significant changes in melatonin, 5‐HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.
Twenty‐four hour rhythms of serum prolactin, growth hormone and luteinizing hormone levels, and of medial basal hypothalamic corticotropin‐releasing hormone levels and dopamine and serotonin metabolism in rats neonatally administered melatonin
Authors: Esquifino Ana I. , Arce Aguslin , Villanua Maria A. , Cardinali Daniel P. 
Published: February 2007

Esquifino AI, Arce A, Villanúa MA, Cardinali DP. Twenty‐four hour rhythms of serum prolactin, growth hormone and luteinizing hormone levels, and of medial basal hypothalamic corticotropin‐releasing hormone levels and dopamine and serotonin metabolism in rats neonatally administered melatonin. J. Pineal Res. 1997; 22:52–58. © Munksgaard, CopenhagenAbstractTo obtain information on long‐term circadian consequences of administering melatonin neonatally to rats, we assessed the 24‐hour rhythms of 1) serum prolactin (PRL), luteinizing hormone (LH), and growth hormone (GH), and 2) medial basal hypothalamic dopamine (DA) and serotonin (5‐HT) metabolism and corticotropin‐releasing hormone (CRH) content in 60‐day old male rats injected with 100 μg of melatonin on the 5th day of life. Controls receiving vehicle alone showed serum PRL concentration (when 60 days of age) attaining its maximum at the end of the light period (i.e., at 2000 hr), while in melatonin‐injected rats high PRL values were found between 1200 and 2000 hr. Twenty‐four hour changes in serum LH levels exhibited a maximum at noon, and to a similar extent in vehicle‐ and melatonin‐treated rats. Neonatal melatonin injection did not affect serum GH concentration when the rats were adult. In the medial basal hypothalamus (MBH), the dihydroxyphenyl acetic acid (DOPAC)/DA ratio attained a maximum at midnight, its amplitude being significantly higher in melatonin‐ than in vehicle‐treated rats. Neonatally melatonin‐injected rats also exhibited a second maximum in DOPAC/DA ratio at noon, coinciding with a minimum in DA levels of MBH. The 5‐hydroxyindoleacetic acid (5‐HIAA)/5‐HT ratio in MBH showed significant diurnal variations in vehicle‐injected controls with maxima at 1200 and 0400 hr, while in melatonin‐treated rats a single maximum occurred at 2400 hr. These maxima correlated with minima in 5‐HT content of MBH. Neonatal melatonin injection brought about a significant increase in the CRH content of MBH, as well as distortion of its diurnal rhythmicity, a maximum being found at noon in controls and at 1800 hr in melatonin‐treated rats. The results indicate that exposure to melatonin early in life affects subsequent diurnal rhythmicity of PRL release, and of DA and 5‐HT turnover and CRH content in the MBH of rats.
Effects of melatonin on mammary gland lesions in transgenic mice overexpressing N‐rasproto‐oncogene
Authors: Mediavilla M.D. , Giiezmez A. , Ramos S. , Kothari L. , Garijo F. , Barceló E.J. Sanchez 
Published: February 2007

Mediavilla MD, Güezmez A, Ramos S, Kothari L, Garijo F, Sanchez Barcelo EJ. Effects of melatonin on mammary gland lesions in transgenic mice overexpressing N‐ras proto‐oncogene. J. Pineal Res. 1997; 22:86–94. © Munksgaard, Copenhagen.AbstractThe oncostatic effects of melatonin on the mammary gland have been studied in transgenic mice carrying the N‐ras proto‐oncogene under the control of the MMTV‐LTR. Female (4‐week‐old) virgin mice with positive transgenic pedigrees were injected with melatonin (200 μg/mouse/ day, five times a week) or vehicle late in the evening. After 5 months of treatment, animals were sacrificed and the mammary glands were dissected for whole mounts, histology, and immunohistochemical analysis with a mouse monoclonal antibody specific for N‐ras protein. Mammary glands of control transgenic mice showed different densities of hyperplastic alveolar nodules (HANs) consisting primarily of dysplastic epithelial cells with nuclear atypia and prominent nucleoli. The epithelial cells of HANs showed a high expression of N‐ras while no immunostaining was detected in the unaffected mammary parenchyma. Only one (10%) of the control transgenic mice presented an infiltrating ductal carcinoma with the neoplastic cells overexpressing N‐ras protein. The mammary glands of melatonin treated mice had a lower density of HANs, absence of epithelial dysplastic cells, and weak immunostaining of N‐ras protein in comparison to the vehicle‐treated group. None of the melatonin treated animals developed mammary carcinomas during the observation period. The lymph nodes of the inguinal mammary glands of all the vehicle‐treated transgenic mice presented hyperplasia and two animals even had lymphomas, whereas in melatonin‐treated animals there was less hyperplasia (two cases were atrophic) and a lack of lymphomas. We conclude that in the mammary glands of MMTV‐LTR/N‐ras transgenic female virgin mice, melatonin a) reduces the incidence of HANs and the expression of N‐ras protein in focal hyperplastic lesions, b) completely prevents the development of epithelial cell atypia and mammary adenocarcinomas, and c) also reduces the hyperplasia of the mammary lymphoid tissue and prevents the development of lymphomas.
The role of melatonin and L‐tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin
Authors: Brzozowski Tomasz , Konturek Peter Ch. , Konturek Stanislaw J. , Pajdo Robert , Bielanski Wladyslaw , Brzozowska Iwona , Stachura Jerzy , Hahn Eckhart G. 
Published: February 2007

Brzozowski T, Konturek PCh, Konturek SJ, Pajdo R, Bielanski W, Brzozowska I, Stachura J, Hahn EG. The role of melatonin and L‐tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. J. Pineal Res. 1997; 23:79–89. ©Munksgaard, CopenhagenAbstractMelatonin, a pineal hormone, synthesized from L‐tryptophan, is known to exist in the gut and to scavenge oxygen free radicals but its role in gastroprotection against acute lesions induced by various strong irritants has been little studied. In this study, we determined the effects of melatonin and L‐tryptophan on gastric secretion and the formation of acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), stress, and ischemia‐reperfusion (I/R). Area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using a H2‐gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentration by specific radioimmunoassay. Intragastric (ig) administration of melatonin (2.5–10 mg/kg) or L‐tryptophan (25–200 mg/kg) failed to affect gastric lesions by ethanol and ASA but dose‐dependently reduced the lesions provoked by stress and I/R; this protective effect was accompanied by a significant rise in plasma melatonin level, GBF, and DNA synthesis and by a marked fall in blood free radicals. L‐tryptophan, which significantly elevated the plasma melatonin by about 3–5‐fold, also reduced the stress and I/R‐induced lesions and blood levels of free radicals, while increasing the GBF, DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE2 by indomethacin abolished the protection and the rise of GBF afforded by melatonin and L‐tryptophan, whereas pretreatment with NG‐nitro‐L‐arginine (L‐NNA), to suppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L‐tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hyperemia probably mediated by endogenous prostaglandin but not NO.
The effect of atenolol, a p!‐adrenergic antagonist, on nocturnal plasma melatonin secretion: Evidence for a dose‐response relationship in humans
Authors: Nathan Pradeep J. , Maguire Kay R , Burrows Graham D. , Norman Trevor R. 
Published: February 2007

Nathan PJ, Maguire KP, Burrows GD, Norman T.R. The effect of atenolol, a β1‐adrenergic antagonist, on nocturnal plasma melatonin secretion: Evidence for a dose‐response relationship in humans. J. Pineal Res. 1997; 23:131–135. © Munksgaard, CopenhagenAbstractPineal β1‐adrenergic receptors are involved in the regulation of melatonin secretion. The involvement of β1adrenergic receptors has been demonstrated by the ability of acute administration ofβ‐antagonists to suppress the nocturnal rise of circulating melatonin and its urinary metabolite 6‐sulphatoxymelatonin (aMT6s). The present study was undertaken to examine the relationship between increasing doses of atenolol and nocturnal plasma melatonin concentrations. Six healthy subjects participated in the study for a period of 5 weeks. Subjects were administered placebo, 12.5, 25, 37.5, and 50 mg doses of atenolol in a randomized single blind design. Each dose was separated by a 1 week washout period. Blood samples were collected at regular intervals from 19.00 hr to 06.00 hr. Repeated measures analysis of variance showed a dose‐dependent decrease in plasma melatonin concentrations (P < 0.01). A Student Newman‐Keuls post hoc test indicated significant differences between placebo and all doses of atenolol (P < 0.05). The results demonstrate a dose‐dependent relationship between β1‐receptor blockade and suppression of nocturnal plasma melatonin in humans.
Use of a newly developed technique to isolate rat pinealoeytes and study the effects of adenosine agonists on melatonin production
Authors: Nicholls Julia , Skene Debra J. , Hourani Susanna M.O. 
Published: February 2007

Nicholls J, Skene DJ, Hourani SMO. Use of a newly developed technique to isolate rat pinealoeytes and study the effects of adenosine agonists on melatonin production. J. Pineal Res. 1997; 23:164–168. © Munksgaard, CopenhagenAbstractRecent studies have suggested a role for adenosine in the regulation of rat pineal melatonin synthesis. The data, however, are conflicting and therefore the aim of this study was to characterize adenosine receptors more fully in vitro by using a range of selective adenosine agonists and the adenosine antagonist 8‐sulphophenyltheophylline (8‐SPT). A simple method for the mechanical separation of rat pinealoeytes was developed. Pinealoeytes were briefly (15 min) incubated with drugs followed by a 4 hr drug‐free incubation period after which melatonin concentrations in the incubation medium were measured by radioimmunoassay. The β‐adrenoceptor agonist isoprenaline gave a dose‐related increase in melatonin production, demonstrating that this pinealocyte preparation technique is suitable to evaluate the effect of drugs on pineal melatonin synthesis. Our results show that adenosine, N6‐(phenylisopropyl)adenosine (R‐PIA) and 2‐p‐(2‐carboxethyl) phenethylamino‐5 '‐N‐ethylcarboxamidoadenosine (CGS21680) did not affect melatonin synthesis alone or in combination with isoprenaline. However 5'‐N‐ethylcarboxamidoadenosine (NEC A) (100 uM) potentiated the stimulatory effect of isoprenaline (3 μM) on pineal melatonin production and this effect appeared to be antagonized by 8‐SPT (50 uM). These results are consistent with activation by NECA of an A2b adenosine receptor.
Alterations in F‐actin distribution in cells treated with melatonin
Authors: Matsui Denise Hitomi , Machado‐Santelli Gláucia Maria 
Published: February 2007

Matsui DH, Machado‐Santelli G.M. Alterations in F‐actin distribution in cells treated with melatonin. J. Pineal Res. 1997; 23:169–175. © Munksgaard, CopenhagenAbstractOne of the possible pathways of action of melatonin is its effect on the cytoskeleton. In this work we looked for alterations in the cytoskeleton of cells treated with melatonin at physiological concentrations. T‐47D, Hs‐578T (human breast carcinoma cell lines), and MDCK (normal dog kidney) cells were maintained in MCDB 153 supplemented with 1% fetal bovine serum (FBS), or in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% FBS and treated with melatonin (10‐‐9M or 10‐‐10M) for 2 and 5 days, with or without 10‐‐8 M estradiol. F‐actin was stained with phalloidin‐fluorescein isothiocyanate (FITC). Cytokeratin 19 and β‐tubulin filaments were detected with specific monoclonal antibodies and secondary antibodies bound to FITC. Melatonin‐treated T‐47D cells observed in a transmission electronic microscope (TEM) showed an irregular nuclear shape and intermediate filaments disposed around the nucleus, which was not observed in control cells. Immunofluorescence analysis of cytokeratin filaments did not show significant differences between their distribution in control and treated cells. Melatonin did not induce significant alterations in cytokeratin filaments of T‐47D, Hs578T or MDCK cells in DMEM and MCDB 153, or T‐47D cells in DMEM. Melatonin induced the derangement of F‐actin both in T‐47D and MDCK cells kept in MCDB 153. The same was not observed when estradiol was also present. We did not observe significant alterations in the distribution of F‐actin in T‐47D or Hs‐578T cells grown in DMEM. In DMEM, melatonin‐treated MDCK cells were more elongated, with a slight concentration of F‐actin on the cell boundary. Melatonin induced very slight alterations in microtubule organization of all cell lines studied.
Effects of sympathicolytic and sympathomimetic drugs on plasma immunoreactive melatonin in the domestic pig
Authors: Lewczuk Bogdan , Przybylska‐Gornowicz Barbara 
Published: February 2007

Lewczuk B, Przybylska‐Gornowicz B. Effects of sympathicolytic and sympathicomimetic drugs on plasma immunoreactive melatonin in the domestic pig. J. Pineal Res. 1997; 23:209–220. © Munksgaard, CopenhagenAbstractPlasma immunoreactive melatonin was monitored for 110 hr in sexually immature female domestic pigs kept under 12L:12D light conditions and treated with two sympathicolytic (α‐methyl‐p‐tyrosine, propranolol) and three sympathicomimetic (clorgyline, isoproterenol, dobutamine) drugs. Mean levels of plasma melatonin in the control pigs showed significant diurnal changes with the highest values during the scotophase. In the individual gilts the diurnal changes of plasma melatonin were markedly irregular; melatonin increases were not consistently noted at night, and melatonin levels during light and darkness varied considerably between days. The lack of consistency in the diurnal patterns of plasma melatonin in individual pigs during consecutive days explains the large inter‐individual differences observed in previous short‐term studies. Administration of α‐methyl‐p‐tyrosine resulted in the decrease in both daytime and nighttime melatonin levels, compared with the control group, but it did not eliminate the increases in melatonin during the night. Treatment with other drugs did not significantly change the level of plasma melatonin compared with the control group, however they had modulatory effects on melatonin rhythm. The results suggest that the plasma melatonin in the domestic pig is controlled by the adrenergic nervous system, but the pharmacology of the secretion and/or metabolism of this pineal hormone is different than described in other species.
Comparison of the antioxidant activity of melatonin and pinoline in vitro
Authors: Pähkla Rein , Zilmer Mihkel , Kullisaar Tiiu , Rägo Lembit 
Published: February 2007

Pahkla R, Zilmer M, Kullisaar T, Rago L. Comparison of the antioxidant activity of melatonin and pinoline in vitro. J. Pineal Res. 1998; 24:96–101. © Munksgaard, CopenhagenAbstractSeveral recent experiments have shown that melatonin is an efficient antioxidant and free radical scavenger. In the present study the antioxidative effect of melatonin was compared with that of pinoline. Pinoline (6‐methoxy‐tetrahydro‐β‐carboline) can be formed in the mammalian body under physiological conditions from 5‐hydroxytryptamine or as a tricyclic metabolite of melatonin. Both melatonin and pinoline inhibited lipid peroxidation and showed comparable activity in a total antioxidant status test. Melatonin and pinoline concentration‐dependently scavenged hydroxyl radicals with IC5011.4±1.0 (J.M for melatonin and 62.3±3.8 uM for pinoline. These results support the importance of the indolic part of the molecule and the 5‐methoxy group common to both compounds in terms of the ability of these molecules to quench the hydroxyl radicals. As pinoline has been shown to exert an antidepressant‐like effect in behavioral experiments and has been reported to have a low toxicity, this compound should be further studied as a potential antidepressant with pronounced antioxidative effects. These results further support the importance of pineal gland in antioxidative protection. Rein Pahkla,1 Mihkel Zilmer,2 Tiiu Kullisaar,2 and Lembit Rago1 Departments of 'Pharmacology and biochemistry, University of Tartu, EE2400 Tartu, Estonia
Postnatal developmental changes in NSE and NNE mRNA expression in the rat pineal gland: In situ hybridization histochemistry
Authors: Feng Xue‐Lian , Usui Hiroshi , Fujita Toshiya , Ichikawa Tomio , Katagiri Takashi , Washiyama Kazuo , Kumanishi Toshiro 
Published: February 2007

Feng X‐L, Usui H, Fujita T, Ichikawa T, Katagiri T, Washiyama K, Kumanishi T. Postnatal developmental changes in NSE and NNE mRNA expression in the rat pineal gland: In situ hybridization histochemistry. J. Pineal Res. 1998; 24:108–116. © Munksgaard, CopenhagenAbstractBy in situ hybridization, neuron‐specific enolase (NSE) and non‐neuronal enolase (NNE) mRNAs were examined in the rat pineal gland at the postnatal developmental and adult stages. The distributions of hybridized signals were analyzed in comparison with immunohistochemical staining of synaptophysin (SYN), which is a marker for pinealocytes. In SYN‐positive areas that were observed throughout postnatal developmental and adult stages, we detected both NSE and NNE signals, which increased simultaneously during early postnatal development and thereafter became stationary. Quantitative analysis revealed that NNE signals were 2‐ to 3‐fold greater in number than NSE signals at any given stage. This predominant expression pattern of NNE differed from that in neurons, which usually showed both signals at similar levels and seemed to reflect the difference in physiological function from neurons. During the early postnatal stages, a cord‐like arrangement of cells without distinct SYN staining was observed. This arrangement was the thickest at postnatal day 0 and became dispersed and thinner with development, showing a relationship with formation of vascularized connective tissue stroma. By in situ hybridization, many of the constituent cells showed weak NNE signals but no distinct NSE signals. However, some cells also showed weak NSE signals, suggesting heterogeneity of these cells. The characteristic NSE and NNE expression patterns in the pineal gland cells clarified in this study might provide a basis for further studies of the differentiation and function of the pineal gland.