Ca2+ signals evoked by histamine H1 receptors are attenuated by activation of prostaglandin EP2 and EP4 receptors in human aortic smooth muscle cells

BACKGROUND AND PURPOSE Histamine and prostaglandin E-2 (PGE(2)), directly and via their effects on other cells, regulate the behaviour of vascular smooth muscle (VSM), but their effects on human VSM are incompletely resolved. EXPERIMENTAL APPROACH The effects of PGE(2) on histamine-evoked changes in intracellular free Ca2+ concentration ([Ca2+](i)) and adenylyl cyclase activity were measured in populations of cultured human aortic smooth muscle cells (ASMCs). Selective ligands of histamine and EP receptors were used to identify the receptors that mediate the responses. KEY RESULTS Histamine, via H-1 receptors, stimulates an increase in [Ca2+](i) that is entirely mediated by activation of inositol 1,4,5-trisphosphate receptors. Selective stimulation of EP2 or EP4 receptors attenuates histamine-evoked Ca2+ signals, but the effects of PGE(2) on both Ca2+ signals and AC activity are largely mediated by EP2 receptors. CONCLUSIONS AND IMPLICATIONS Two important inflammatory mediators, histamine via H-1 receptors and PGE(2) acting largely via EP2 receptors, exert opposing effects on [Ca2+](i) in human ASMCs.