Associates' Presentations
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Lymphocyte-conditioned medium enhances Ca?+ current in the posterior pituitary: Implications for SIADH.

R.A. Wilke, M.D./Ph.D. (Associate); D. Hildeman, Ph.D.; K. Pederson; D. Muller, M.D./Ph.D.; M.B. Jackson, Ph.D., University of Wisconsin, Madison.

States of profound inflammation are known to influence fluid and electrolyte homeostasis through an increase in the release of neurohypophysial peptides. Recent data suggest that inflammatory cytokines can increase serum levels of antidiuretic hormone (ADH). In an effort to define this immune-neuroendocrine interaction mechanistically, we designed several experiments to monitor the excitability of neurohypophysial axon terminals while perfusing them with lymphocyte-conditioned medium. In the past, the small size and inaccessibility of these peptidergic nerve terminals has impeded progress in understanding their secretory function. However, with the recent application of patch clamp technology to the rat neurohypophysis, we have gained considerable insight into the membrane events governing the release of ADH under a variety of physiologic and pathologic conditions.

Supernatant harvested from mouse T-Cell culture medium causes a reversible increase in neurohypophysial calcium current. Control medium has no such effect. Interestingly, the potentiating effect of the lymphocyte-conditioned medium can be inactivated by heat (100?CC for 30 minutes prior to superfusion). Taken collectively, these data suggest that some soluble factor released by the T-Cell line is capable of enhancing neurohypophysial ADH release through a selective increase in calcium influx. Such an interaction could very well be responsible for the clinical "syndrome of inappropriate ADH secretion (SIADH)" which accompanies many severe inflammatory processes. Further electrophysiologic studies designed to characterize this phenomenon might eventually lead to the development of novel therapeutic strategies for controlling it.


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