LTD4 increases cytosolic free calcium and inositol phosphates in human neutrophils: inhibition by the novel LTD4 receptor antagonist, SR2640, and possible relation to modulation of chemotaxis.

LTD4 increased the level of free intracellular calcium ([Ca++]i) and stimulated the production of inositol phosphates (IP) in human polymorphonuclear neutrophils (PMN). Calcium was predominantly mobilized from intracellular pools. After a single stimulus, the cells were refractory to a second challenge with the same concentration of LTD4, but the calcium response to LTB4 was normal. The rise in [Ca++]i as well as the stimulated production of IP was inhibited by the novel LTD4 antagonist, SR2640. SR2640 also abolished the attenuation by LTD4 of LTB4-directed PMN chemotaxis. The results suggest that human PMN contain specific LTD4 receptor that trigger phosphatidyl inositol hydrolysis by activation of phospholipase C, leading to intracellular calcium mobilization, which may be involved in modulation of chemotaxis.