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.