The phospholipid growth factors (PLGFs), including lysophosphatidic acid (LPA), have been implicated in corneal wound healing. PLGF concentrations and activities are elevated after corneal injury. Using real-time PCR, we quantified receptor mRNA levels in the healing rabbit cornea. In intact corneas, transcripts for S1P(1), LPA(1), and LPA(3) receptor subtypes were detected, as was lipid phosphate phosphatase 1 (LPP1). After wounding, the trend for endothelium and keratocytes was for significant decreases in transcript numbers for the three receptor subtypes, whereas epithelial cells showed increased transcript numbers, except for an S1P(1) decrease in healing cells. LPP1 transcript numbers were decreased in keratocytes and endothelium, although LPP-specific activity was unchanged. LPA-elicited Ca(2+) transients were significantly reduced in the healing endothelium. Consistent with reduced LPA(3) receptor numbers, dioctylglycerol pyrophosphate, a selective antagonist, reduced LPA-induced Ca(2+) transients 2.7-fold in nonwounded epithelium but only 1.5-fold in wound-healing endothelium. These data for the first time establish physiologically relevant differential changes in the expression of PLGF receptor subtypes and provide evidence for the changing role of LPA(3) receptors in endothelial cells.