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Neurohypophyseal Hormones: From Genomics and Physiology to Disease

IL-1 directly excites isolated rat supraoptic neurons via upregulation of the osmosensory cation current

Centre for Research in Neuroscience, Montreal General Hospital and McGill University, Montreal, Quebec, Canada

Submitted 7 October 2005 ; accepted in final form 9 November 2005

Previous studies have shown that IL-1 can excite the magnocellular neurosecretory cells (MNCs) of the hypothalamus. However, it is not known whether IL-1 can have direct IL-1 receptor type 1 (IL-1R1)-mediated effects on MNCs, and little is known about the cellular mechanisms by which IL-1 influences electrical activity in these cells. Here, we used patch-clamp recordings to examine the effects of IL-1 on acutely isolated rat MNCs. We found that IL-1 directly excites MNCs in a dose-dependent manner and that this response can be blocked by an inhibitor of the IL-1R1. Voltage-clamp analysis of the current evoked by IL-1 revealed a linear current-voltage relationship between –90 and –20 mV, and a reversal potential near –35 mV. This value was not affected by reducing the concentration of chloride ions in the external solution, indicating the involvement of a nonselective cation conductance. The effects of IL-1 were inhibited by Na-salicylate, an inhibitor of cyclooxygenase. Moreover. the effects of IL-1 were mimicked and occluded by PGE₂, and were inhibited by AH-23848, an antagonist of the PGE₂ type 4 (i.e., EP₄) receptor. The current evoked by IL-1 was also abolished by 100 µM gadolinium (Gd³⁺), but was significantly larger when examined in cells preshrunk by negative pressure applied via the recording pipette. IL-1 alone did not cause changes in cell volume nor in the mechanosensitivity of MNCs. We conclude that IL-1 directly excites MNCs via an IL-1R1-mediated induction of PGE₂ synthesis and EP₄ receptor-dependent autocrine upregulation of the nonselective cation conductance that underlies osmoreception.

vasopressin; prostaglandin; EP₄ receptor; osmosensitivity; neurohypophysis