Lysophospholipid receptor-mediated calcium signaling in human keratinocytes.
The lysophospholipids, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), stimulate chemotaxis and induce differentiation of human keratinocytes. As Ca(2+) plays an important role in keratinocyte differentiation, we studied Ca(2+) signaling by S1P and LPA in these cells, known to express mRNA transcripts of the S1P(1-5) and LPA(1-3) receptors, and the receptor subtypes involved in this process. S1P and LPA caused transient increases in intracellular free Ca(2+) concentration ([Ca(2+)](i)), with pEC(50) values of 8.5+/-0.11 and 7.5+/-0.23, respectively. The [Ca(2+)](i) increases are apparently mediated by stimulation of phospholipase C and involve Ca(2+) mobilization from thapsigargin-sensitive stores and subsequent Ca(2+) influx. The LPA-induced [Ca(2+)](i) increases were not inhibited by the LPA(1/3) receptor antagonist, dioctanoylglycerol pyrophosphate. The S1P-induced [Ca(2+)](i) increases were largely inhibited by the putative S1P(3) antagonist, BML-241, and the S1P(1/3) antagonist, VPC23019. The S1P(1)-specific agonist, SEW2871, did not increase [Ca(2+)](i) but stimulated chemotaxis of keratinocytes, which was fully blocked by S1P(1) antisense oligonucleotides. The data indicate that LPA and S1P potently increase [Ca(2+)](i) in human keratinocytes and that the effect of LPA is mediated by LPA(2), whereas that of S1P is mediated at least to a large part by S1P(3). The S1P(1) receptor, without stimulating [Ca(2+)](i) increases, mediates chemotaxis of keratinocytes.
Lichte
Karin
K
Institut für Pharmakologie, Universität Duisburg-Essen, Essen, Germany.
Rossi
Roberto
R
Danneberg
Kerstin
K
ter Braak
Michael
M
Kürschner
Ulrich
U
Jakobs
Karl H
KH
Kleuser
Burkhard
B
Meyer zu Heringdorf
Dagmar
D
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002465:Cell Movement; D002633:Chemotaxis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008954:Models, Biological; D049312:Receptors, Lysophospholipid / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
C515031:BML 241; D008246:Lysophospholipids; D049312:Receptors, Lysophospholipid; D049349:Receptors, Lysosphingolipid; D053778:Thiazolidines; D049452:Green Fluorescent Proteins; C060506:sphingosine 1-phosphate; D019284:Thapsigargin; D010738:Type C Phospholipases; D013110:Sphingosine; C032881:lysophosphatidic acid; D002118:Calcium