CHRONIC REGULATION OF THE NA H ANTIPORTER

This review focuses on studies from our laboratory investigating the m echanisms of chronic regulation of the Na/H antiporter in renal and no nrenal cells. Tissue culture provides an ideal tool for investigating this problem because it avoids many complicating effects that would oc cur in an intact animal during a chronic study. Chronic decreases in e xtracellular fluid pH cause an increase in Na/H antiporter activity th at is dependent on protein synthesis and associated with an increase i n NHE-1 (isoform of the sodium-hydrogen antiporter) mRNA abundance. Th is effect is associated with acid-induced increases in a number of imm ediate early genes, including c-fos, c-jun, junB, and egr-1. In primar y cultures of rabbit proximal tubule cells, activation of protein kina se C for 2 hours causes an increase in Na/H antiporter activity that p ersists 24 hours later, is dependent on transcription and translation, and is associated with an increase in NHE-1 mRNA abundance. Chronic a ctivation of protein kinase A in opossum kidney (OKP) cells causes an increase in Na/H antiporter activity that persists 16 to 20 hours late r and is dependent on protein synthesis. This latter effect is of part icular interest because it is opposite in direction to the acute inhib itory effect of protein kinase A on the Na/H antiporter in these cells .