RNA-SYNTHESIS INHIBITORS INCREASE MELATONIN PRODUCTION IN Y79 HUMAN RETINOBLASTOMA CELLS

Y79 human retinoblastoma cells synthesize melatonin in cell culture th us providing a unique preparation for studying the regulation of melat onin biosynthesis in mammalian retinas. We have previously demonstrate d that Y79 cells express NAT and HIOMT activity and produce melatonin in a cAMP- and protein synthesis-dependent manner by increasing NAT, a nd not HIOMT activity, as has been demonstrated in other retinal and p ineal melatonin synthesizing systems. We have extended these studies t o investigate the role of RNA synthesis in melatonin regulation, and r eport here that RNA synthesis inhibitors do not suppress melatonin pro duction in Y79 retinoblastoma cells. Rather, at intermediate concentra tions, the inhibitors actinomycin D and camptothecin increase melatoni n levels. Camptothecin, a topoisomerase I inhibitor, also increased NA T activity and accumulated cAMP levels in a calcium-dependent manner. This effect on cAMP did not appear to occur through phosphodiesterase, and other regulators of retinal melatonin such as melatonin degradati on or components of the dopamine system were unaffected. These results are in contrast with the suppression of melatonin synthesis by RNA sy nthesis inhibitors observed in rat and chick pineal glands and in chic k retinas.