HORMONAL-REGULATION OF RENAL INORGANIC-PHOSPHATE TRANSPORT IN THE WINTER FLOUNDER, PLEURONECTES-AMERICANUS

Intestinal uptake and renal excretion are the primary determinants of inorganic phosphate (P-i) balance in teleosts. In general, teleost kid neys may either reabsorb filtered P-i or secrete excess P-i into the u rine. Primary monolayer cultures of flounder (Pleuronectes americanus) renal proximal tubule epithelium (PTCs) have helped identify several hormones that may participate in conservation or excretion of P-i. Mou nted in Ussing chambers, the monolayer cultures can be used to assay t ransepithelial P-i transport. Several factors, including metabolic aci dosis, elevation of plasma [P-i], salmon stanniocalcin, salmon somatol actin and mammalian prolactin, have now been shown to alter transepith elial P-i transport in winter flounder PTCs. Salmon stanniocalcin (STC ) stimulated P-i luminal-to-peritubular transport (reabsorption) at a dosage of 12.5-50 ng/ml (0.25-1.0 nM). Net P-i transport changed withi n 30 min and progressively increased from slight net secretion in untr eated controls to net reabsorption after 3 h. The target and function of somatolactin have been uncertain. In our hands salmon somatolactin (sSL) also stimulated P-i reabsorption by flounder PTCs in a dose-depe ndent manner at physiological levels of the hormone (12.5 ng/ml). Net P-i transport was significantly altered by sSL within 2 h after the in itial exposure. Neither sSL nor STC had any effect on transepithelial Ca2+ transport. The effects of both sSL and STC were mimicked by forsk olin, whereas H-89, a highly specific protein kinase A inhibitor, sign ificantly decreased the effects of the hormones as well as forskolin-i nduced P-i reabsorption. Furthermore, the production and release of cA MP were increased more than two-fold following exposure to STC or sSL. The data indicate that STC and sSL directly stimulate net renal P-i r eabsorption by a cAMP-dependent pathway. In addition, mammalian prolac tin greatly, and salmon growth hormone slightly, increased net P-i rea bsorptive flux, whereas salmon prolactin had no effect. These results appear to be related to the location of the cysteine disulfide bonds w ithin the molecular structure. Although somatolactin and stanniocalcin may both stimulate renal P-i conservation, their actions may be relat ed to different physiological conditions.