title: Histamine-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells.
abstract: Agonist stimulation of human pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) with histamine showed similar spatiotemporal patterns of Ca(2+) release. Both sustained elevation and oscillatory patterns of changes in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) were observed in the absence of extracellular Ca(2+). Capacitative Ca(2+) entry (CCE) was induced in PASMC and PAEC by passive depletion of intracellular Ca(2+) stores with 10 microM cyclopiazonic acid (CPA; 15-30 min). The pyrazole derivative BTP2 inhibited CPA-activated Ca(2+) influx, suggesting that depletion of CPA-sensitive internal stores is sufficient to induce CCE in both PASMC and PAEC. The recourse of histamine-mediated Ca(2+) release was examined after exposure of cells to CPA, thapsigargin, caffeine, ryanodine, FCCP, or bafilomycin. In PASMC bathed in Ca(2+)-free solution, treatment with CPA almost abolished histamine-induced rises in [Ca(2+)](cyt). In PAEC bathed in Ca(2+)-free solution, however, treatment with CPA eliminated histamine-induced sustained and oscillatory rises in [Ca(2+)](cyt) but did not affect initial transient increase in [Ca(2+)](cyt). Furthermore, treatment of PAEC with a combination of CPA (or thapsigargin) and caffeine (and ryanodine), FCCP, or bafilomycin did not abolish histamine-induced transient [Ca(2+)](cyt) increases. These observations indicate that 1) depletion of CPA-sensitive stores is sufficient to cause CCE in both PASMC and PAEC; 2) induction of CCE in PAEC does not require depletion of all internal Ca(2+) stores; 3) the histamine-releasable internal stores in PASMC are mainly CPA-sensitive stores; 4) PAEC, in addition to a CPA-sensitive functional pool, contain other stores insensitive to CPA, thapsigargin, caffeine, ryanodine, FCCP, and bafilomycin; and 5) although the CPA-insensitive stores in PAEC may not contribute to CCE, they contribute to histamine-mediated Ca(2+) release.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla 92093-0725, USA.
authors.forename: Joseph R H
authors.initials: JR
authors.lastname: Mauban
authors.forename: Katherine
authors.initials: K
authors.lastname: Wilkinson
authors.forename: Christian
authors.initials: C
authors.lastname: Schach
authors.forename: Jason X-J
authors.initials: JX
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007476:Ionophores; D018942:Macrolides; C057620:bafilomycin A; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D019284:Thapsigargin; D006632:Histamine; D002118:Calcium; C000543:cyclopiazonic acid