L. Parravicini

Bio: L. Parravicini is an academic researcher from University of Milan. The author has contributed to research in topics: Melatonin & Pineal gland. The author has an hindex of 2, co-authored 2 publications receiving 95 citations.

Action of morphine on melatonin release in the rat.

Abstract: Some data from the literature raised the possibility of an interaction between the opioidergic system and pineal secretion. The present study was undertaken in order to investigate the acute influence exerted by opioids upon plasma melatonin levels in the albino rat. Different doses of morphine hydrochloride were injected (1, 1.5, 2, 3 mg/kg) intraperitoneally into anaesthetized adult male rats bearing a cannula previously inserted into the carotid. Blood samples were collected subsequently at 30-min intervals, within a period of 90 min following drug administration. Plasma melatonin contents were determined by a radioimmunoassay (RIA) method. Acute administration resulted in a dose-dependent increase in plasma melatonin concentration when compared to the respective controls. This effect is blocked by pretreatment with Naloxone. The present result seem to support the hypothesis that the opioidergic system, in certain circumstances, might contribute to the activation of melatonin secretion.

Effect of an acute injection of melatonin on the basal secretion of hypophyseal hormones in prepubertal and pubertal healthy subjects.

Abstract: It is well known that the pineal gland can modulate the secretion of pituitary hormones. Melatonin, the main hormone produced by the pineal gland, acts at the hypothalamic site, whereas hypophyseal sensitivity to melatonin seems to change with age. To investigate the influence of pubertal development on the role of the pineal gland in the regulation of the secretion of pituitary hormones, FSH, LH, Prl, TSH and GH responses to melatonin were evaluated in a group of 9 prepubertal and 10 pubertal healthy subjects of both sexes. Melatonin was given im at a dose of 0.2 mg/kg body weight at 3 p.m. Venous blood samples were drawn -20, 0, 20, 40, 60, 90, 120, 180 and 240 min, after melatonin injection. According to the same experimental protocol, venous blood samples were collected during a saline infusion on a separate occasion. FSH, LH, Prl, TSH and GH plasma levels were measured with RIA. In pubertal subjects, a significant rise in the mean Prl levels was seen 90 min after melatonin as compared with those during saline infusion. The Prl melatonin response area was significantly lower in prepubertal treated subjects and significantly higher in pubertal ones compared with the respective controls. The mean GH values showed a significant decrease 120 min after melatonin only in prepubertal subjects; no significant variations were seen in 8 of 10 pubertal subjects, whereas in the last 2 a marked increase was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Abstract: Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

Melatonin and sleep in humans.

Abstract: Early studies on the physiological effects of melatonin typically reported hypnotic 'side-effects'. Later studies, specifically addressing this action, failed to reliably replicate hypnotic effects using standard polysomnography. This difference may be related to differences in the basic physiological action of melatonin compared with more conventional hypnotics. It is suggested that melatonin exerts a hypnotic effect through thermoregulatory mechanisms. By lowering core body temperature, melatonin reduces arousal and increases sleep-propensity. Thus, in humans, one role of melatonin is to transduce the light-dark cycle and define a window-of-opportunity in which sleep-propensity is enhanced. As such, melatonin is likely to be an effective hypnotic agent for sleep disruption associated with elevated temperature due to low circulating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep disorders related to the inappropriate timing of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production (e.g., beta-blockers and benzodiazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration.

Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis.

Abstract: Objective Melatonin is involved in the regulation of the sleep-wake cycle and exhibits multiple interactions with the neuroendocrine and the immune system. Melatonin secretion in healthy individuals follows a stable circadian rhythm. Critical illness, continuous administration of drugs, and loss of

Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients.

Abstract: Background: Sleep disturbance is common in intensive care patients. Aside from its unpleasantness, there is a correlation with intensive care unit (ICU) syndrome/delirium. Reasons for sleep deprivation appear to be multifactorial, including the underlying illness, an acute superimposed disturbance, medications, and the ICU environment itself. There are reasons to believe that alterations of the 'biological clock' might contribute. Melatonin secretion is one reflection of this internal sleep/wake mechanism. Melatonin levels are normally high during the night and low during daytime, being suppressed by bright light. Methods: Melatonin levels in blood and urine were studied over 3 consecutive days in eight critically ill patients during deep sedation and mechanical ventilation. Sedation was assessed with the sedation-agitation (SAS) scale and bispectral index (BIS) monitor. Results: The circadian rhythm of melatonin release was abolished in all but one patient, who recovered much more quickly than the others. There was no correlation between melatonin levels and levels of sedation. Conclusions: This study indicates that dyssynchronization of the melatonin secretion rhythm is common in critically ill and mechanically ventilated patients. It could be hypothesized that an impairment of the melatonin rhythm may play a role in the development of sleep disturbances and delirium in intensive care patients, and that melatonin supply could reduce the incidence of these phenomena.

Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men.

Abstract: Summary Objective Older adults are less responsive to the phase-shifting effects of light than younger subjects and may have difficulties adapting to abrupt time shifts. This study aims to determine whether the potent melatonin agonist agomelatine (S-20098) is capable of phase-shifting overt circadian rhythms in older adults. Subjects and design Eight healthy elderly men participated in a double-blind, two-period, cross-over study of 15 days of daily administration of either agomelatine (50 mg) or placebo at 1830 h. Measurements At the end of each treatment period, the 24-h profiles of body temperature and of the plasma levels of GH, PRL, cortisol and TSH were collected and sleep was monitored polygraphically. Results Phase-advances, averaging nearly 2 h, were observed for the temperature profile and for the variables characterizing the temporal organization of cortisol secretion following agomelatine administration. A similar trend was observed for the circadian rise of plasma TSH. There was no effect of agomelatine on any of the sleep variables. Agomelatine stimulated GH secretion during the wake period and was associated with a transient elevation of PRL levels. Conclusions Melatonin agonists such as agomelatine may be useful to phase-shift at least some overt circadian rhythms in older adults.