Serotonin agonists increase transferrin levels via activation of 5-HT1C receptors in choroid plexus epithelium.
Choroid plexus epithelial cells are enriched in mRNA for proteins such as the iron carrier transferrin, which acts as a trophic factor in the brain. Choroid plexus epithelial cells also have a high density of 5-HT1C receptors linked to activation of the phosphoinositide (PI) hydrolysis second messenger system. The present studies show that the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) potently increases PI hydrolysis and the levels of transferrin in primary cultures of rat choroid plexus epithelial cells. These effects are blocked by the 5-HT1C/5-HT2 receptor antagonists mesulergine and mianserin, but not by the 5-HT2 receptor-selective antagonist spiperone. Similarly, mesulergine and mianserin, but not spiperone, block the increases in transferrin levels and PI hydrolysis elicited by 5-carboxamidotryptamine (5-CT), a 5-HT1 receptor-selective agonist, and by serotonin. We conclude, therefore, that 5-HT1C receptor activation in the choroid plexus leads to an increase in the production of transferrin. By promoting transferrin synthesis in the choroid plexus, 5-HT may indirectly influence brain development and differentiation.
Esterle
T M
TM
Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
Sanders-Bush
E
E
D000591:Amino Acid Isomerases / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000378:metabolism*; D003524:Cyclosporins / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase; D010716:Phosphatidylinositols / Q000378:metabolism; D015347:RNA Probes; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism*
D002352:Carrier Proteins; D003524:Cyclosporins; D004873:Ergolines; D010716:Phosphatidylinositols; D015347:RNA Probes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014168:Transferrin; D008803:Mianserin; D012701:Serotonin; D013134:Spiperone; C047087:5-carboxamidotryptamine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; C031649:mesulergine; D013936:Thymidine