TY - JOUR
T1 - Insulin induces internalization of the 5-HT2A receptor expressed in HEK293 cells
AU - Ohkura, Masamichi
AU - Tanaka, Naoko
AU - Kobayashi, Hideyuki
AU - Wada, Akihiko
AU - Nakai, Junichi
AU - Yamamoto, Ryuichi
PY - 2005/7/25
Y1 - 2005/7/25
N2 - To visualize the 5-hydroxytryptamine2A (5-HT2A) receptor, we developed a 5-HT2A receptor fused with yellow fluorescent protein (5-HT2A-YFP) and expressed this receptor in HEK293 cells. In 5-HT2A-YFP-expressing cells, but not in YFP-expressing or non-expressing cells, 5-HT induced a transient increase in the intracellular Ca2+ concentration (Ca2+ transient) in the Fluo 3 assay, suggesting that 5-HT2A-YFP possesses a function similar to the wild-type 5-HT2A receptor. Interestingly, not only 5-HT but also insulin induced the internalization of 5-HT2A-YFP. Insulin also inhibited the 5-HT-induced Ca2+ transient. Genistein, an inhibitor of tyrosine kinase, blocked these insulin effects. Our results provide the first evidence that insulin receptor signaling via tyrosine kinase activation induces internalization of the plasma membrane 5-HT2A receptor, and demonstrate crosstalk between the 5-HT2A receptor and the insulin receptor.
AB - To visualize the 5-hydroxytryptamine2A (5-HT2A) receptor, we developed a 5-HT2A receptor fused with yellow fluorescent protein (5-HT2A-YFP) and expressed this receptor in HEK293 cells. In 5-HT2A-YFP-expressing cells, but not in YFP-expressing or non-expressing cells, 5-HT induced a transient increase in the intracellular Ca2+ concentration (Ca2+ transient) in the Fluo 3 assay, suggesting that 5-HT2A-YFP possesses a function similar to the wild-type 5-HT2A receptor. Interestingly, not only 5-HT but also insulin induced the internalization of 5-HT2A-YFP. Insulin also inhibited the 5-HT-induced Ca2+ transient. Genistein, an inhibitor of tyrosine kinase, blocked these insulin effects. Our results provide the first evidence that insulin receptor signaling via tyrosine kinase activation induces internalization of the plasma membrane 5-HT2A receptor, and demonstrate crosstalk between the 5-HT2A receptor and the insulin receptor.
KW - 5-HT receptor
KW - Ca transient
KW - Insulin
KW - Internalization
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UR - http://www.scopus.com/inward/citedby.url?scp=22044440325&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.06.011
DO - 10.1016/j.ejphar.2005.06.011
M3 - Article
C2 - 15979608
AN - SCOPUS:22044440325
VL - 518
SP - 18
EP - 21
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -