DIMETHYL-SULFOXIDE INHIBITS RENAL NA plus -K plus -ATPASE AT A SITE DIFFERENT FROM OUABAIN AND ATRIAL PEPTIDES

The present investigation was designed to determine 1) if dimethyl sulfoxide (DMSO) inhibits renal cortical and medullary Na+-K+-ATPase at the ouabain binding site and 2) if this inhibition of Na+-K+-ATPase by DMSO involves atrial natriuretic peptides or prostaglandins. DMSO (10%) inhibited renal cortical and medullary Na+-K+-ATPase 31% and 29.5%, respectively. Ouabain (0.5 mM) inhibited renal cortical and medullary Na+K+-ATPase 32% and 35%, respectively. When DMSO and ouabain were added together the inhibition of renal cortical and medullary Na+-K+-ATPase was 55% and 59%, respectively. Atrial natriuretic peptides consisting of amino acids 1-30 (i.e., long acting natriuretic peptide), 31-67 (vessel dilator), 79-98 (kaliuretic peptide) and 99-126 (atrial natriuretic factor, ANF) of the 126 amino acid ANF prohormone inhibited renal cortical Na+-K+-ATPase 27.5%, 20%, 37.5% and 0% at a 10(-11)M concentration. The addition of DMSO caused a doubling (P<0.05) of this inhibition. Likewise, these same atrial peptides inhibited renal medullary Na+-K+-ATPase 27.8%, 19.2%, 39.5%, and 0% with DMSO doubling (P<0.05) their Na+-K+-ATPase inhibition. There was not any additive effect of any of the atrial peptides with ouabain. Naproxen, a prostaglandin inhibitor, completely blocked atrial peptides and ouabain's inhibition of Na+-K+-ATPase but not DMSO's. Each of the atrial peptides except ANF increased prostaglandin E(2) synthesis while DMSO did not increase prostaglandin E(2) synthesis. This investigation suggests that DMSO has its inhibiting effect at a site different from the ouabain binding site on renal Na+-K+-ATPase since it has an additive effect with ouabain in inhibiting Na+-K+-ATPase while the atrial peptides appear to have their effect at the ouabain binding site. As opposed to the atrial peptides, DMSO's mechanism of inhibiting Na+-K+-ATPase does not appear to involve prostaglandin E(2).