New pharmacological aspects of melatonin

Detta är en avhandling från Linköping : Linköpings universitet

Sammanfattning: Melatonin is a hormone that takes part in the regulation of biological rhythms. It is produced in the pineal gland and is stimulated by darkness and inhibited by exposure to light. The increased amouot of melatonin during the hours of darkness sends a chronobiological message throughout the body, and translates it into a chemical message that can be read by target cells. This process requires that a receiving protein, a receptor, is present on the cell surface, and that it can recognize melatonin and transfer the signal from outside of the cell to the inside, where it can be transformed into a cellular response. The present investigation was focused on receptor recognition, receptor activation and receptor-mediated signaling.The scales of the cuckoo wrasse (Labrus ossifagus L.), a teleost fish, bear melanophores that contain pigment granules that can be transported to the center of the cell (pigment aggregation) or distributed throughout the melanophore (pigment dispersion). Pigment aggregation is governed by sympathetic nerve endings that stimulate an α2-adrenoceptor, and also by circulating hormones, for example melatonin. To answer questions regarding receptor interactions, melatonin was used in the melanophore bioassay.The results show that melatonin did not induce pigment aggregation when administrated alone. The hormone did, however, reinforce aggregation induced by noradrenaline, which reveals a melatonin-noradrenaline synergism. Pharmacological studies were performed to elucidate this synergism. Data obtained using α2-adrenoceptor and melatonin receptor ligands, and by investigating intracellular mediators, indicate that, hypothetically, the noradrenaline-melatonin synergism may be due to the existence of an α2-adrenergic receptor with two functional sites: one site for catecholamines, such as noradrenaline, and a second "modulatory" site for melatonin.It is known that smooth muscle cells from pregnant human myometrium express adrenoceptors and that labor tends to begin during the dark hours. The effect of melatonin on myometrial contractility was examined in order to investigate if the same synergism appeares in the myometrium as in the melanophores. The contractility of biopsied myometrial samples taken from women undergoing cesarean sections was measured in vitro. The results show that melatonin alone did not increased myometrial contractility, but it did reinforce noradrenaline-induced contraction, i.e. a melatonin-noradrenaline synergism. Consequently, it is possible that the greater production of melatonin at night induces increased myometrial contractility that leads to the beginning of labor.

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