Melatonin Receptors In The Kidney And Other Peripheral Tissues
PINEAL UPDATE: FROM MOLECULAR MECHANISMS TO CLINICAL IMPLICATIONS(1997)
Abstract
Along with the better established sites of melatonin action such as the brain and retina, direct melatonin actions on tissues such as the pituitary and a variety of peripheral tissues are seen. Membrane binding sites have been defined using I-125-iodomelatonin in the gastrointestinal tract, vas deferens, kidneys, vasculature, lung and heart, as well as in the testes, ovary, adrenal glands and immune tissues. These putative melatonin receptors have the high affinity, saturability, reversibility, low density and pharmacologic specificity required for a hormone with the low circulating levels which are demonstrated by melatonin. Moreover, melatonin receptor genes have been cloned which, when expressed, have the characteristics of the membrane receptors seen in these various tissues. We have recently shown that melatonin receptor mRNAs are expressed not only in chicken brain but also in kidney. Melatonin membrane receptors in the CNS seem to be coupled to an inhibitory G-protein. Melatonin binding in human and chicken kidney, guinea pig and pigeon spleen and chicken testes and lung is sensitive to treatment with guanosine 5'-O-(3-thiotriphosphate), and in some of these peripheral tissues it has been shown that melatonin treatment within the physiologic range inhibits activation of cAMP by forskolin. Among mammals diurnal variation with a decrease in binding density at the beginning of the dark phase is found in rat brain, anterior pituitary, pars tuberalis and hamster Harderian gland. These findings support a functional role for these binding sites outside the central nervous system, and suggest that we are now only at the beginning of understanding the peripheral actions of melatonin.
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