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.