Sphingosine 1-phosphate (S1P) induces shape change in rat C6 glioma cells through the S1P2 receptor: development of an agonist for S1P receptors.
Treatment with isoprenaline led to a change in the cell morphology of rat C6 glioma cells. This morphological change was reverted by the addition of sphingosine 1-phosphate (S1P). Using this morphological change as a response marker we determined that DS-SG-44 ((2S,3R)-2-amino-3-hydroxy-4-(4-octylphenyl)butyl phosphoric acid) was an agonist of S1P receptors. The DS-SG-44-induced morphological reversion was not observed with such structurally related molecules as DS-SG-45 ((2S,3R)-2-amino-3-hydroxy-4-(3-octylphenyl)butyl phosphoric acid) and DS-SG-12 ((2S,3R)-2-amino-4-(4-octylphenyl)butane-1,3-diol). The S1P- and DS-SG-44-induced shape changes were neither reproduced with the S1P1/S1P3 receptor agonist VPC24191 nor inhibited by the S1P1/S1P3 receptor antagonist, VPC23019. Transfection with small interfering RNA (siRNA) for the S1P2 receptor greatly inhibited the DS-SG-44-induced shape change, and in part an S1P-induced response. In the presence of VPC23019, siRNA transfection for the S1P2 receptor almost completely blocked the S1P- and DS-SG-44-induced shape changes. Our results suggested that DS-SG-44, a newly-synthesized S1P analogue, acted as an S1P receptor agonist and that the S1P-induced shape change in rat C6 glioma cells was mediated mainly through the S1P2 receptor, and cooperatively through the S1P1/S1P3 receptors.
Kim
Kyeok
K
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Research Institute for Drug Development, Pusan National University, Busan 609-735, Republic of Korea.
Kim
Yu-Lee
YL
Sacket
Santosh J
SJ
Kim
Hyo-Lim
HL
Han
Mijin
M
Park
Deok Seong
DS
Lee
Baeck Kyoung
BK
Lee
Won Koo
WK
Ha
Hyun-Joon
HJ
Im
Dong-Soon
DS
D000704:Analysis of Variance; D000818:Animals; D048430:Cell Shape / Q000187:drug effects*; D005910:Glioma; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C523263:((2S,3R)-2-amino-3-hydroxy-4-(4-octylphenyl)butyl phosphoric acid); D008246:Lysophospholipids; D010756:Phosphoric Acids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine