TY - JOUR
T1 - Intracellular signaling involved in estrogen regulation of serotonin reuptake
AU - Koldzic-Zivanovic, Nina
AU - Seitz, Patricia K.
AU - Watson, Cheryl
AU - Cunningham, Kathryn A.
AU - Thomas, Mary L.
N1 - Funding Information:
We would like to thank Dr. Scott Whittemore for providing RN46A cells and Dr. Leoncio Vergara for his help with Ca 2+ measurement experiments. This research was supported by NIDA grants DA11428 and DA00260.
PY - 2004/10/29
Y1 - 2004/10/29
N2 - 17β-Estradiol (E 2) regulates neuronal activity via genomic and rapid, non-genomic mechanisms. The rat serotonergic neuronal cell line (RN46A) was used to investigate the rapid effects of E 2 on serotonin (5-HT) reuptake and on potential intracellular signaling pathways. RN46A cells express the serotonin transporter (SERT) and estrogen receptor (ER)β, but not ERα. Fifteen minute E 2 treatment (10 -9 M) decreased 5-HT uptake. Intracellular cAMP levels were not increased by 15 min E 2 treatment; however, E 2 caused an increase in intracellular Ca 2+ levels, with a maximum response within the first minute. The response was E 2 specific, since other steroids (17α-estradiol, testosterone, and progesterone) had no effect. The ER antagonist ICI 182,780 blocked the rapid E 2 effects on intracellular Ca 2+ levels as did the selective ER modulator tamoxifen. In summary, changes in intracellular Ca 2+ levels caused by E 2 and mediated through ERβ may be responsible for observed rapid effects of E 2 on SERT activity.
AB - 17β-Estradiol (E 2) regulates neuronal activity via genomic and rapid, non-genomic mechanisms. The rat serotonergic neuronal cell line (RN46A) was used to investigate the rapid effects of E 2 on serotonin (5-HT) reuptake and on potential intracellular signaling pathways. RN46A cells express the serotonin transporter (SERT) and estrogen receptor (ER)β, but not ERα. Fifteen minute E 2 treatment (10 -9 M) decreased 5-HT uptake. Intracellular cAMP levels were not increased by 15 min E 2 treatment; however, E 2 caused an increase in intracellular Ca 2+ levels, with a maximum response within the first minute. The response was E 2 specific, since other steroids (17α-estradiol, testosterone, and progesterone) had no effect. The ER antagonist ICI 182,780 blocked the rapid E 2 effects on intracellular Ca 2+ levels as did the selective ER modulator tamoxifen. In summary, changes in intracellular Ca 2+ levels caused by E 2 and mediated through ERβ may be responsible for observed rapid effects of E 2 on SERT activity.
KW - Calcium
KW - Estrogen
KW - Non-genomic effects
KW - RN46A cells
KW - Serotonin transporter
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U2 - 10.1016/j.mce.2004.07.017
DO - 10.1016/j.mce.2004.07.017
M3 - Article
C2 - 15489003
AN - SCOPUS:5644294412
SN - 0303-7207
VL - 226
SP - 33
EP - 42
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -