5-HT-induced transferrin production by choroid plexus epithelial cells in culture: role of 5-HT1c receptor.
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)
Tsutsumi
M
M
Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee.
Sanders-Bush
E
E
D000818:Animals; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014168:Transferrin / Q000096:biosynthesis*
D010716:Phosphatidylinositols; D011719:Pyrazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014168:Transferrin; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D008238:Lysergic Acid Diethylamide