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5-HT-induced transferrin production by choroid plexus epithelial cells in culture: role of 5-HT1c receptor

M Tsutsumi and E Sanders-Bush

Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee.

Previous studies in our laboratory have demonstrated that serotonin (5- HT) elevates transferrin production by choroid plexus epithelial cells in primary culture in a time- and concentration-dependent fashion. The present study shows that 5-HT stimulates phosphoinositide hydrolysis in these cells and further demonstrates that the phosphoinositide hydrolysis response is mediated by the 5-HT1c receptor. To determine if the effect on transferrin is also mediated by the 5-HT1c receptor, the effects of 5-HT receptor agonists and antagonists were examined in choroid plexus epithelial cells in primary culture. The stereoisomers of lysergic acid diethylamide (LSD) and the piperazine derivative 6- chloro-2-[1-piperazinyl]-piperazine (MK-212) were evaluated as potential agonists. MK-212 and (+)LSD mimicked 5-HT, increasing transferrin levels to the same extent. The levorotary isomer, (-)LSD, had no effect. This agonist profile agrees with that previously found for 5-HT1c receptor-mediated phosphoinositide hydrolysis. Three antagonists with varying potencies to block 5-HT1c receptor-mediated phosphoinositide hydrolysis were examined: ritanserin, mianserin and spiperone. The results of these studies were less clear-cut. Neither mianserin nor ritanserin significantly reduced the effects of 5-HT on transferrin, even though they markedly reduced 5-HT-induced phosphoinositide hydrolysis. Consistent with its low potency at the 5- HT1c receptor, spiperone, a 5-HT2 and 5-HT1a antagonist, was a less effective antagonist of the phosphoinositide hydrolysis response than were ritanserin and mianserin. Spiperone also failed to block the effect of 5-HT on transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 254, Issue 1, pp. 253-257, 07/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.