Mechanisms mediating osmoreception: Sustained response in the tilapia cell model

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Osmoregulation is fundamental to life in complex organisms. The structure and function of molecules that control the processes of life are maintained by weak forces (hydrophobic interactions and hydrogen bonds) and thus are sensitive to small changes in their ionic and osmotic environment. For this reason, organisms invest considerable energy in controlling intracellular and extracellular fluids. In fish, for example, osmoregulation typically consumes 25-50% of total metabolic output. Beyond this, osmotic equilibrium is a fragile balance that is maintained through the continuous interplay of a major portion of the neuroendocrine array. Indeed, a persistently difficult challenge in clinical medicine is the regulation of salt and water balance in seriously ill patients. In view of the cost and importance of osmoregulation, it may seem ironic that the mechanisms that monitor and control salt and water balance in vertebrates are so poorly understood. Closer attention, however, reveals the impediment: the typically complex structure and arrangement of osmoreceptive cells and tissues. In virtually all cases, one cannot simultaneously measure changes in cell size and the osmoregulatory output (hormone release) in a cell that can be distinguished specifically as osmoreceptive cells. In teleost fish, prolactin (PRL) is an essential osmoregulatory hormone that maintains hydromineral balance in fresh water and whose secretion is controlled directly by extracellular osmolality. Consistent with these actions, plasma PRL is elevated in the tilapia, Oreochromis mossambicus, a euryhaline teleost, in fresh water and PRL release is stimulated when extracellular osmolality declines. Our previous NSF-supported studies demonstrated that a fall in extracellular osmolality leads to the passive influx of water into the PRL cell that increases cell volume within minutes. This initiates an influx of extracellular Ca2+ through stretch-activated channels, producing a rise in intracellular calcium [Ca2+]i which stimulates PRL release. This rapid response is extended under sustained stimulation in vitro with increased PRL release being observed for 24 h in hyposmotic medium. On the other hand, PRL release is reduced under hyperosmotic conditions, reflecting its counteraction to salt water osmoregulation. However, signal transduction mechanisms that underlie the osmotic control of sustained PRL release and gene expression are not known. In fact, very little is known about the cellular mechanisms that transduce either acute or chronic osmotic information in any osmoregulatory endocrine system. The present work is aimed at characterizing cellular mechanisms by which extended exposure to physiological changes in ambient osmolality evoke sustained changes in PRL release and gene expression using the tilapia PRL cell model. These studies will provide new insight into the cell-signaling mechanisms that mediate the sustained alteration of the release and production of osmoregulatory hormones that at present cannot be obtained with other model systems. This work will involve students at many levels from high school to graduate students, including several underrepresented minorities, who will be trained in an important area of research, which will have an impact in cell physiology.