Melatonin and its receptors: Biological function in circadian sleep‐wake regulation (original) (raw)
Indian journal of biochemistry & biophysics, 2008
Melatonin (N-acetyl-5-methoxytryptamine) was first purified and characterized from the bovine pineal gland extract by Aron Lerner and co-workers in 1958. Since then, a plethora of information has piled up on its biosynthesis, metabolism, time-bound periodicity, physiological and patho-physiological functions, as well as its interactions with other endocrine or neuro-endocrine organs and tissues in the body. Melatonin has wide range of applications in physiology and biomedical fields. In recent years, a significant progress has been made in the understanding mechanism of its actions at the cellular and molecular levels. Consistent efforts have uncovered the mystery of this indoleamine, and demonstrated its role in regulation of a large as well as diverse body functions in different groups of animals in general, and in humans in particular. Current review, in commemoration of 50 years of discovery of melatonin, while revisiting the established dogmas, summarizes current information on...
Egyptian Journal of Basic and Applied Sciences, 2015
Antiepileptic Antiosteoporotic Antioxidant Cardiovascular disease Circardian rhythm Hypnotic Immunodulatory Melatonin a b s t r a c t Melatonin is one of the most versatile and ubiquitous molecule widely distributed in nature has been reported to play a role in a wide variety of physiological responses including reproduction, circadian homeostasis, sleep, retinal neuromodulation, and vasomotor responses. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light ⁄ dark cycle via the suprachiasmatic nucleus. Melatonin is synthesized in all areas of the body such as gastrointestinal tract, skin, bone marrow, retina and in lymphocytes, from which it may influence other physiological functions through paracrine signalling. In addition to regulation of circadian rhythm of melatonin a variety of other physiological effects such as hypnotic, antidepressant, antiepileptic, oncostatic, immunomodulatory, antiosteoporotic, in cardiovascular disease, neuromodulatory and cerebral ischaemic condition have been reported.
Recent developments in research of melatonin and its potential therapeutic applications
British Journal of Pharmacology, 2018
This Themed section was prompted by a symposium at the annual meeting of the British Pharmacological Society held, in London, in 2016. It was obvious that the session had barely scratched the surface of what has been discovered about the pharmacodynamics of melatonin and that a Themed section on this compound in the British Journal of Pharmacology was long overdue. As will become clear, melatonin has a wide range of actions, only some of which are mediated by melatonin receptors (MT 1 and MT 2); others include free-radical scavenging as well as targets on mitochondrial membranes and the cell nucleus. Melatonin was first discovered over a century ago, and it is more than 50 years since its isolation from pineal tissue extracts and the first report that its production follows a circadian rhythm. That aspect of its function has attracted a great deal of attention: most members of the lay public are aware that melatonin comes out at night (it is known as the 'Dracula hormone'), and some people take it to sort out their jet lag, despite the scepticism about its beneficial effects for that indication. What is less well known is that other aspects of health and disease, such as neurodegeneration, diabetes or cancer, are also influenced by melatonin, either directly or indirectly. This collection of articles draws attention to this diverse spectrum of actions and explains the underlying mechanisms, insofar as that is possible. To start on familiar territory, Zisapel (2018) updates the evidence for regulation of sleep rhythms by melatonin. Whereas the suprachiasmatic nucleus (SCN) is the 'metronome' for the circadian cycle (and many other aspects of internal body state, such as thermoregulation and autonomic arousal), melatonin is a major contributor to the process of entraining its rhythmic activity. Secretion of this hormone from the pineal is influenced by light, and it serves as a signal for 'darkness', even in nocturnal animals. This hormone prevents arousal, which is mediated by the SCN, and promotes (but does not induce) sleep. Zisapel (2018) discusses
Dual sources of melatonin and evidence for different primary functions
Frontiers in endocrinology, 2024
This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells.
A brief review about melatonin, a pineal hormone
2018
Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions. Arch Endocrinol Metab. 2018;62(4):472-9
Melatonin: pharmacology, functions and therapeutic benefits
Current neuropharmacology, 2016
Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing. First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, various physiological effects of melatonin are reviewed, including detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Given these physiological effects, potential benefits of melatoni...
Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders
Cellular and Molecular Neurobiology
Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by antiexcitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans.