Role of intra- and extracellular calcium stores in mesothelial cell response to histamine

Abstract

Ca2+ may play an important role in mesothelial cellular responses because Ca2+ acts as an intracellular messenger in a wide variety of cellular responses in different tissues. The present study was designed to clarify the mechanisms of cytosolic Ca2+ mobilization in the mesothelial cells. Rat pleural and pericardial mesothelial cells were maintained in vitro, and the Ca2+ movement was evaluated using fura 2. Histamine (30 microM to 10 mM) induced a biphasic elevation of intracellular levels of Ca2+ concentration ([Ca2+]i) that consisted of a rapid initial transient elevation followed by a sustained elevation. Neither removal of extracellular Ca2+ nor inhibition of Ca2+ influx by 1 microM nifedipine affected the histamine-induced initial transient elevation of [Ca2+]i in mesothelial cells. Nifedipine did not block histamine-induced sustained elevation of [Ca2+]i. KCl (25 and 50 mM) elicited a biphasic elevation of [Ca2+]i. However, this KCl-induced elevation of [Ca2+]i was abolished by nifedipine treatment. Ryanodine (10 microM) induced a transient elevation of [Ca2+]i in Ca(2+)-free solution. The histamine-induced elevation of [Ca2+]i was completely blocked by H1-receptor antagonists. These results suggest that the mesothelial cells have three pathways to increase [Ca2+]i: release from intracellular Ca2+ stores, Ca2+ influx through L-type voltage-dependent Ca2+ channels, and receptor-operated Ca2+ channels.