Mechanisms and control of intestinal and renal sulfate secretion in marine teleosts

Date of Completion

January 2004


Biology, Animal Physiology




Marine teleosts, which maintain their plasma osmotic pressure below that of the surrounding marine environment, continually imbibe seawater to counteract dehydration. Seawater contains high levels of SO42− (25 mM), and excess SO42− is acquired through ingestion. Renal excretion, primarily through proximal tubular secretion, removes this SO42− burden. While it is generally accepted that the gastrointestinal tract is the avenue for excess absorption, the exact location and mechanism is not known. Data presented in this thesis shows that while the anterior intestine passively absorbs SO4 2−, an active secretory component dependent on metabolism and the plasma membrane Na+ gradient is also present. Active secretion is facilitated by an electroneutral brush border SO42− /Cl exchanger and is abolished by satiety (i.e., full stomach). It is hypothesized that active intestinal SO4 2− secretion functions in maintenance of SO4 2− homeostasis and water absorption. ^ A basolateral SO42−/OH exchanger and a brush border anion exchanger with affinities for both luminal HCO3 and Cl facilitate active renal tubular SO42− secretion. Tubular SO42− secretion is dependent on carbonic anhydrase (CA) and is stimulated by cortisol. To further examine this relationship, the effect of cortisol on CA-dependent SO42− secretion by primary monolayer cultures of flounder proximal tubule cells (fPTCs) was examined. Cortisol was found to increase tubular CA enzymatic activity, CA isoform II protein expression, and CA-dependent SO4 2− secretion. Thus, regulation of CA expression may provide cortisol with a level of control over renal tubular SO4 2− secretion. ^ The uptake of SO42− across the basolateral membrane of proximal tubule cells is dependent on the plasma membrane Na + gradient and facilitated by SO42−/OH exchange prompting an investigation of the role of Na +/H+ exchange (NHE) and the effect of interstitial acidification (metabolic acidosis). Metabolic acidosis stimulated tubular SO42− secretion in fPTCs and the intact animal. In fPTCs, the stimulation caused by metabolic acidosis was dependent on CA and brush border Na+/H+ exchange (NHE) activity. NHE isoforms 1, 2, and 3 were identified in proximal tubule cells, and induction of one or all of these NHEs may be required for enhanced renal tubular SO 42− secretion during metabolic acidosis. ^