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 E2 (PGE2 ), 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 PGE2 on histamine-evoked changes in intracellular free Ca(2+) concentration ([Ca(2+) ]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 H1 receptors, stimulates an increase in [Ca(2+) ]i that is entirely mediated by activation of inositol 1,4,5-trisphosphate receptors. Selective stimulation of EP2 or EP4 receptors attenuates histamine-evoked Ca(2+) signals, but the effects of PGE2 on both Ca(2+) signals and AC activity are largely mediated by EP2 receptors. CONCLUSIONS AND IMPLICATIONS Two important inflammatory mediators, histamine via H1 receptors and PGE2 acting largely via EP2 receptors, exert opposing effects on [Ca(2+) ]i in human ASMCs.