Histamine H1 receptor-stimulated Ca2+ signaling pathway in human periodontal ligament cells.
We studied histamine-induced Ca2+ mobilization in human periodontal ligament (HPDL) cells. Histamine induced a transient rise in intracellular Ca2+ ([Ca2+]i) and maintained a sustained phase in the presence of extracellular Ca2+. In the absence of extracellular Ca2+, the transient peak was slightly reduced and the sustained phase was decreased to the basal level. The initial rise in [Ca2+]i was attributed to two components: intracellular Ca2+ release and Ca2+ influx, whereas the sustained phase was due to Ca2+ influx. After depletion of intracellular Ca2+ stores with thapsigargin, a known Ca(2+)-ATPase inhibitor, histamine-induced increase in [Ca2+]i was significantly reduced, suggesting histamine induces Ca2+ release from inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]- and thapsigargin-sensitive Ca2+ stores. Histamine-induced peak in [Ca2+]i was increased dose-dependently in the presence and absence of extracellular Ca2+. The histamine-mediated response in [Ca2+]i was specifically attenuated by chlorpheniramine (H1 antagonist) but not by cimetidine (H2 antagonist), clearly indicating that activation of H1 receptor mediates histamine-induced Ca2+ mobilization. We next examined the effect of histamine on inositol phosphates formation. Histamine stimulated the formation of inositol phosphates which changed time-dependently. In particular, the formation of Ins(1,4,5)P3 was increased significantly for 10 s. The histamine-induced Ca2+ mobilization caused an increase of prostaglandin E2 (PGE2) release which was reduced in excluding extracellular Ca2+. These results indicate that activation of histamine H1 receptor induces the accumulation of Ins(1,4,5)P3 and the following transient increase in [Ca2+]i, and elicits the release of PGE2 which may be coupled with Ca2+ influx.
Niisato
N
N
Research Institute of Oral Science, Nihon University, Matsudo, Japan.
Ogata
Y
Y
Furuyama
S
S
Sugiya
H
H
D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D013729:Terpenes; D002744:Chlorpheniramine; D019284:Thapsigargin; D002927:Cimetidine; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D015232:Dinoprostone; D002118:Calcium