Transferrin gene expression and synthesis by cultured choroid plexus epithelial cells. Regulation by serotonin and cyclic adenosine 3',5'-monophosphate.
Primary cultures of rat choroid plexus epithelial cells were established and used to investigate the role of the choroid plexus in the synthesis and secretion of transferrin. Transferrin gene expression was determined by a Northern blot analysis with a transferrin cRNA probe. A single transferrin mRNA species was detected and found to be the same size as the transcripts in the liver and Sertoli cells. Immunoprecipitation of radiolabeled secreted proteins with an antiserum transferrin antibody demonstrated that cultured choroid plexus epithelial cells synthesize and secrete a 70-kDa species of transferrin. Levels of transferrin secretion by rat choroid plexus epithelial cells in culture were measured by radioimmunoassay. Treatment of the choroid plexus epithelial cells in culture with cell-permeable cAMP analogs or serotonin led to time- and concentration-dependent changes in the levels of transferrin in the medium. Dibutyryl-cAMP and 8-bromo-cAMP decreased the levels of transferrin synthesized and secreted by choroid plexus epithelial cells with an EC50 value of 30 nM. Serotonin, however, increased the levels of transferrin with an EC50 value of 100 nM. A concomitant change in transferrin mRNA concentrations was observed in response to serotonin. These data suggest that the synthesis of transferrin by the choroid plexus is reciprocally regulated by the neurotransmitter serotonin and by regulatory agents coupled to adenylate cyclase. Regulatory agents such as serotonin may have a critical role in modulating the proteins synthesized by the choroid plexus, thereby influencing the composition of the cerebrospinal fluid.
Tsutsumi
M
M
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Skinner
M K
MK
Sanders-Bush
E
E
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014168:Transferrin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology
D012333:RNA, Messenger; D014168:Transferrin; D012701:Serotonin; D000242:Cyclic AMP