There are multiple regulators of renal proximal tubule sodium-dependent phosphate (Na+-Pi) transport, including 1,25-dihydroxyvitamin D (1,25-Vit. D), parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), and arachidonic acid (AA) and/or its metabolites. The purpose of our studies was to determine whether the effect of these factors on Pi transport is synergistic or antagonistic. The control solution or the substances were added independently or coincidentally to opossum kidney (OK) cells before incubation for 4 h. 1,25-Vit. D (10(-8) M) had no significant effect on Pi transport (up arrow 6.8%; p = 0.8). PTH (10(-7) M) significantly inhibited Pi transport by 39.6% (p < 0.0001). IGF-1 (10(-8) M) stimulated Pi transport by 19.6% (p< 0.0001). The AA metabolite 20-HETE (10(-7) M) had no significant impact on Pi transport (down arrow6.4; p = 0.3). The combined effect of 1,25-Vit. D and PTH was no different from PTH alone (p = 0.2). Likewise, addition of either 1,25-Vit. D or 20-HETE to IGF-1 failed to affect the magnitude of the increase on Pi transport induced by IGF-1 atone (p = 0.4, p = 0.6, respectively). The combination of 20-HETE and PTH was not different from that observed with PTH alone (p = 0.9). We conclude that in OK cells, PTH inhibits whereas IGF-1 stimulates Pi transport into OK cells. The effects of each of these hormones a re independent and unaffected by either 1,25-Vit. D or 20-HETE. Copyright (C) 2001 S. Karger AG, Basel.