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M Coculescu

Publications and source records attributed to M Coculescu.

At least 19 recordsLinked to original sources
PubMed2001

Presence of oxytocinergic neuronal-like cells in the bovine pineal gland: an immunocytochemical and in situ hybridization study.

In the last decade, there is more and more evidence showing the role of the central innervation of the pineal gland, but there are controversies around the intra or extrapineal origin of oxytocin found within the pineal tissue. In order to check the amount and the site of synthesis of oxytocin in the bovine pineal gland, we performed a morphological and chromatographic study. The anatomical distribution of the pineal oxytocin was explored by immunohistochemistry and in situ hybridization for the corresponding mRNA. The results confirm the presence of oxytocinergic fibres in the bovine pineal, some of them endowed with big varicosities. Immunohistochemistry also displayed neuronal-like cells in the pineal body. The in situ hybridization for the mRNA encoding pre-pro/oxytocin-NFZ I used a mixture of three oligonucleotide probes labelled with (35)S. This allowed identification of positive cells in the bovine pineal. The content in oxytocin was evaluated by radioimmunoassay during 5 months, from July to November, and the peptidic extract revealed an increase of pineal oxytocin immunoreactivity in September as compared with July or November. The significance of intrinsic oxytocin innervation of the bovine pineal gland, as well as the threefold increase of the oxytocin content in the pineal in September, remains to be elucidated.

Animals↗
PubMed2001

Melatonin shortens the survival rate of Ehrlich ascites-inoculated mice.

UNLABELLED: OBJECTIVES Pineal gland may have a role in organism's protection against cancer. Melatonin as well as still unidentified low-weight molecular pineal substance(s) have been reported to have growth inhibitory effect on different tumor cells. We tested the influence of melatonin and of a bovine pineal extract on the survival rate of AKR mice inoculated with Ehrlich ascites. The tumor is known to have an accelerated development after pinealectomy. MATERIAL AND METHODS: Male AKR mice, kept under a 14/10 hours - Light /Dark cycle, were inoculated intraperitoneally (i.p.) with 1.5x 10(6) Ehrlich ascites cells. On day three after inoculation the animals were divided in three groups (n=10). Each animal received i.p. daily (20.00H), until their death, 250 microl of solution containing melatonin (250 microg), pineal extract (equivalent of 1 bovine pineal gland) or saline. RESULTS: The average survival rate of the animals treated with melatonin was shorter (14.8+/-2.23 days) compared to control animals (21.9+/-2.21 days)(p=0.01). The animals treated with the pineal extract had a longer survival rate (22.6 +/- 1.8 days) but not statistically significant. The pineal extract was not available for testing at higher doses. CONCLUSION: In our model, melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions.

Animals↗
PubMed1999

Arginine vasotocin mRNA revealed by in situ hybridization in bovine pineal gland cells.

Arginine vasopressin (AVP) is the main antidiuretic hormone in mammals and arginine vasotocin (AVT) in submammalian vertebrates. The possibility that the genetic material encoding AVT is maintained in mammals is controversial. In this study, we investigated by radioactive in situ hybridization the possible presence of the mRNA encoding AVP and AVT, and using immunocytochemistry the presence of structures immunoreactive for AVP and AVT in the bovine pineal gland. In situ hybridization was performed by use of 35S-labelled oligoprobes. Immunocytochemistry was performed using specific polyclonal rabbit antibodies and the avidin-biotin-complex method. In situ hybridization revealed positive signals for both AVP mRNA and AVT mRNA in a few cells scattered throughout the pineal body. Immunocytochemistry revealed thin AVP-immunoreactive fibres in the pineal stalk and the pineal gland. It also revealed staining of several AVT-immunoreactive nerve fibres in both the pineal stalk and the gland. In addition, polyhedral, neuron-like cell bodies from which two to three processes emerged were also AVT-immunoreactive. Thus, our investigation shows the presence of AVP/AVT-immunoreactive cellular structures in the bovine pineal gland. Our data further show the presence of mRNAs encoding both AVT and AVP. We therefore suggest that AVT mRNA is translated into an AVT-like peptide in the bovine pineal.

Animals↗
PubMed1999

A cytotoxic, apoptotic, low-molecular weight factor from pineal gland.

Previous studies suggest that the pineal gland may play a role in tumour growth inhibition. In this respect, melatonin, as the major hormone of this gland, has been extensively studied. However, there is growing evidence for the existence of other yet unknown pineal factors that may have tumour growth inhibiting properties. Here we describe the partial purification of a highly cytotoxic low molecular weight (<400 Da) hydrophilic fraction (designated F2M3R), starting from a porcine pineal extract (PE), via methanol precipitation followed by reverse-phase HPLC. F2M3R is cytotoxic for a highly apoptosis-resistant human erythroleukemia cell line (K562) at a concentration as low as 30 microg/ml. The viability of the cells was not influenced by an identical prepared porcine pituitary extract or by melatonin. PE induces apoptosis in K562 cells as indicated by three different criteria: morphology, in situ TUNEL assay and bi-parametric FACS analysis with annexin V and propidium iodide, but does not influence the viability of stimulated peripheral blood mononuclear cells. These observations warrant further purification and validation of the cytotoxicity in a panel of different human tumour and non-malignant cells.

Animals↗
PubMed1998

Vasopressin neurotransmission and the control of circadian rhythms in the suprachiasmatic nucleus.

Vasopressin (VP) is one of the principal transmitters in the suprachiasmatic nucleus (SCN). Approximately 20% of neurones in the dorsomedial division of the SCN synthesize the peptide and a high proportion of SCN neurones (> 40%) are excited by VP acting through the V1 receptor. This suggests that VP may act as a feedback regulator of electrical activity within the nucleus. Such an intrinsic excitatory signal can be demonstrated by perifusion with a V1 antagonist which reduces spontaneous neural activity. As the synthesis and release of VP occurs in a circadian manner, this leads to a variable feedback excitation which may contribute to the circadian pattern of activity of the neural clock. This role in amplifying rhythmicity is supported by observations that animals deficient in VP show a reduced circadian amplitude of behavioural rhythms (e.g. locomotor and cortical electroencephalographic rhythms). VP expression declines during ageing and although aged animals show no change in the proportion of SCN neurones excited by VP, the rhythm of spontaneous electrical activity shows a progressive decline, consistent with the reduced endogenous excitatory feedback. However, the homozygous Brattleboro rat which lacks any VP expression still maintains rhythms of electrical activity, indicating that VP is not the sole factor generating circadian activity. The generation of this rhythmicity may depend upon the interaction of VP with other transmitter systems, such as the inhibitory transmitters somatostatin and GABA which show a circadian variation in efficacy. In addition to its role in feedback amplification of the endogenous rhythm of electrical activity, VP also functions as part of the efferent signal to the rest of the CNS where it potentially regulates a number of behavioural and physiological rhythms, including the circadian activity of the hypothalamo-pituitary-adrenal axis. Thus, the combined amplification and signalling functions makes VP an important component of the neuronal clock function in mammals.

Animals↗
PubMed1994

The effects of [Arg8]vasopressin and [Arg8]vasotocin on the firing rate of suprachiasmatic neurons in vitro.

The excitatory effect of [Arg8]-vasopressin and its potential contribution to the circadian cycle of electrical activity in the suprachiasmatic nucleus of the rat was investigated using extracellular recordings from hypothalamic slices from virgin female rats. The majority of neurons tested for their responses to vasopressin and [Arg8]-vasotocin displayed coincident, dose-dependent excitation by both peptides, although the relative efficacy varied between neurons, with some showing a highly preferential excitation by vasotocin. Perifusion with the vasopressin receptor antagonist d(CH2)5[Tyr(OEt)2,Val4,Cit8]-vasopressin was able to block the majority of responses to vasopressin or vasotocin (20/25), and similar excitation could be induced by the selective agonist [Phe2,Orn8]-vasotocin, indicating a mainly V1 receptor-mediated effect. Few neurons (3/27; 11%) responded to the oxytocin-specific agonist, [Thr4,Gly7]-oxytocin, suggesting a low occurrence of oxytocin receptors. In addition to blocking the action of exogenous vasopressin, the V1 antagonist caused a reversible suppression of spontaneous basal activity in 7/25 cases, consistent with the presence of an endogenous excitatory vasopressin tone. In agreement with previous reports, the activity of suprachiasmatic nucleus neurons showed a significant correlation between spontaneous activity and the light-dark cycle, with activity decreasing during the subjective dark phase. When neurons were divided on the basis of their response to vasopressin and/or vasotocin, the peptide-sensitive neurons continued to show a strong correlation (r = 0.513, P < 0.01) while the insensitive neurons showed no correlation (r = 0.136, P > 0.05). These data confirm the presence of V1 type receptors in the suprachiasmatic nucleus and also indicate a small number of neurons possessing additional classes of receptor selective for either oxytocin or vasotocin. Contrary to previous reports, they also demonstrate that endogenous vasopressin tonically excites suprachiasmatic nucleus neurons. The fact that vasopressin-sensitive (but not vasopressin-insensitive) neurons show a level of basal activity correlated with time, suggests that this tone may contribute to the circadian cycle of electrical activity in the suprachiasmatic nucleus.

Action Potentials↗
PubMed1982

Gonadotropins in rats with hereditary diabetes insipidus (Brattleboro strain).

In the Brattleboro strain of rats, the genetic defect in vasopressin synthesis seems to be accompanied by a defect in the synthesis of other structurally related nonapeptides, such as the pineal arginine vasotocin which has antigonadotropic properties in animals. It was therefore tempting to investigate gonadotropin secretion in rats with hereditary hypothalamic diabetes insipidus (DI rats).

Animals↗
PubMed1981

Possible hormonal role of the angiotensin-like peptides in mammals' pineal gland.

An isorenin is synthetized in the pineal gland cells. The amount of isorenin as well as the synthesis of angiotensin I and II in the pineal gland depends on the circadian rhythm, osmotic stimuli and stimulation of the cervical sympathetic postganglionar fibres. Pineal angiotensin is released both into the blood and in the cerebrospinal fluid (CFS). The major site of the pineal angiotensin action are the circumventricular organs, the preiventricular receptors of the anterior hypothalamus and the epiphysis cerebri itself. Except its participation in regulating arterial pressure and the hydroelectrolytic metabolism, through its central effects on the brain, pineal angiotensin-like peptides also participate in the pool of circulating angiotensin and it may represent Farrell's pineal glomerulotropic factor.

Angiotensin I↗
PubMed1979

Influence of arginine vasotocin administration on nocturnal sleep of human subjects.

Arginine vasotocin (AVT) or placebo were subcutaneously administered to 4 men at 22.00 and 01.00 h, along four nights, and polygraphic recordings were performed between 22.00 and 02.00 h during sleep. AVT significantly increased only the amount of rapid eye movement (REM) sleep (p less than 0.05), but did not influence the latency of the first REM sleep period. This effect of AVT was not dose dependent in the range between 2 and 12 microgram AVT. AVT or placebo were also intravenously injected or perfused to 10 normal adult subjects, at different times of the day, under clinical control. Doses between 2 microgram perfused 4 h and 12 microgram perfused 30 min, did not produce clinical signs of sleep. It is suggested that AVT is not a blood factor for inducing of slow waves sleep (SWS) or REM sleep in humans.

Adult↗