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Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells.
Biochem J 2001; 353(Pt 1):139-146BJ

Abstract

Exogenous sphingosine 1-phosphate (S1P) increased cytosolic Ca(2+) concentration, stimulated thymidine incorporation (DNA synthesis) and inhibited cell migration in rat aortic smooth-muscle cells (AoSMCs). Although exogenous sphingosine, a substrate of sphingosine kinase or a precursor of S1P, markedly induced the intracellular accumulation of S1P, the lipid failed to mimic the S1P-induced actions. In contrast, dihydrosphingosine 1-phosphate (DHS1P), an S1P receptor agonist, duplicated these S1P actions even though DHS1P was approx. 20-50-fold less potent than S1P. The pharmacological properties of DHS1P for the S1P receptor subtypes Edg-1, Edg-3, Edg-5 and Edg-6 were compared in Chinese hamster ovary (CHO) cells that were overexpressing the respective receptor. In these S1P-receptor-overexpressing cells, DHS1P was approx. 20-30-fold less potent than S1P for the displacement of [(3)H]S1P binding and inositol phosphate response in Edg-5-expressing CHO cells, as was the case for AoSMCs. However, it was slightly (not more than 3-fold) less potent than S1P in cells expressing Edg-1, Edg-3 or Edg-6. Of the above-mentioned four types of S1P receptor, Edg-5 was abundantly expressed in AoSMCs, as demonstrated by Northern blotting. These results suggest that the intracellular accumulation of S1P is not necessary for the S1P-induced Ca(2+) response, for the stimulation of DNA synthesis or for the inhibition of cell migration. Thus these S1P-induced actions might be mediated through extracellular (or cell-surface) S1P receptors in AoSMCs: Edg-5 might be a most important receptor subtype.

Authors+Show Affiliations

Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11115407

Citation

Tamama, K, et al. "Extracellular Mechanism Through the Edg Family of Receptors Might Be Responsible for Sphingosine-1-phosphate-induced Regulation of DNA Synthesis and Migration of Rat Aortic Smooth-muscle Cells." The Biochemical Journal, vol. 353, no. Pt 1, 2001, pp. 139-146.
Tamama K, Kon J, Sato K, et al. Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells. Biochem J. 2001;353(Pt 1):139-146.
Tamama, K., Kon, J., Sato, K., Tomura, H., Kuwabara, A., Kimura, T., ... Okajima, F. (2001). Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells. The Biochemical Journal, 353(Pt 1), pp. 139-146.
Tamama K, et al. Extracellular Mechanism Through the Edg Family of Receptors Might Be Responsible for Sphingosine-1-phosphate-induced Regulation of DNA Synthesis and Migration of Rat Aortic Smooth-muscle Cells. Biochem J. 2001 Jan 1;353(Pt 1):139-146. PubMed PMID: 11115407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells. AU - Tamama,K, AU - Kon,J, AU - Sato,K, AU - Tomura,H, AU - Kuwabara,A, AU - Kimura,T, AU - Kanda,T, AU - Ohta,H, AU - Ui,M, AU - Kobayashi,I, AU - Okajima,F, PY - 2000/12/15/pubmed PY - 2001/3/3/medline PY - 2000/12/15/entrez SP - 139 EP - 146 JF - The Biochemical journal JO - Biochem. J. VL - 353 IS - Pt 1 N2 - Exogenous sphingosine 1-phosphate (S1P) increased cytosolic Ca(2+) concentration, stimulated thymidine incorporation (DNA synthesis) and inhibited cell migration in rat aortic smooth-muscle cells (AoSMCs). Although exogenous sphingosine, a substrate of sphingosine kinase or a precursor of S1P, markedly induced the intracellular accumulation of S1P, the lipid failed to mimic the S1P-induced actions. In contrast, dihydrosphingosine 1-phosphate (DHS1P), an S1P receptor agonist, duplicated these S1P actions even though DHS1P was approx. 20-50-fold less potent than S1P. The pharmacological properties of DHS1P for the S1P receptor subtypes Edg-1, Edg-3, Edg-5 and Edg-6 were compared in Chinese hamster ovary (CHO) cells that were overexpressing the respective receptor. In these S1P-receptor-overexpressing cells, DHS1P was approx. 20-30-fold less potent than S1P for the displacement of [(3)H]S1P binding and inositol phosphate response in Edg-5-expressing CHO cells, as was the case for AoSMCs. However, it was slightly (not more than 3-fold) less potent than S1P in cells expressing Edg-1, Edg-3 or Edg-6. Of the above-mentioned four types of S1P receptor, Edg-5 was abundantly expressed in AoSMCs, as demonstrated by Northern blotting. These results suggest that the intracellular accumulation of S1P is not necessary for the S1P-induced Ca(2+) response, for the stimulation of DNA synthesis or for the inhibition of cell migration. Thus these S1P-induced actions might be mediated through extracellular (or cell-surface) S1P receptors in AoSMCs: Edg-5 might be a most important receptor subtype. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/11115407/Extracellular_mechanism_through_the_Edg_family_of_receptors_might_be_responsible_for_sphingosine_1_phosphate_induced_regulation_of_DNA_synthesis_and_migration_of_rat_aortic_smooth_muscle_cells_ L2 - http://www.biochemj.org/cgi/pmidlookup?view=long&pmid=11115407 DB - PRIME DP - Unbound Medicine ER -