ATRIAL NATRIURETIC PEPTIDE(31-67) INHIBITS NA plus TRANSPORT IN RABBIT INNER MEDULLARY COLLECTING DUCT CELLS - ROLE OF PROSTAGLANDIN-E2

Atrial natriuretic peptide (ANP)(31-67), a portion of the atrial peptide prohormone, circulates in humans, and its plasma level varies with atrial pressure. Like the more widely studied carboxy-terminal fragment ANP(99-126), ANP(31-67) stimulates natriuresis and diuresis. We examined the mechanism of this natriuresis by measuring the effects of ANP(31-67) on Na+ transport in cells of the rabbit inner medullary collecting duct (IMCD). ANP(31-67) (10(-8) M) caused a 26 +/- 4% inhibition of oxygen consumption (QO2); half-maximal inhibition occurred at 10(-11) M, suggesting a physiologic effect. This effect was not additive with either ouabain or amiloride, suggesting that it reflected inhibition of Na+ transport-dependent QO2.ANP(31-67) reduced the amphotericin-induced stimulation of QO2 consistent with inhibition by this peptide of the Na+-K+-ATPase. In addition, ANP(31-67) reduced ouabain-sensitive Rb-86+ uptake under V(max) conditions. Several lines of evidence indicated that PGE2, a known endogenous IMCD Na+-K+-ATPase inhibitor, mediates pump inhibition by ANP(31-67). Thus, ANP(31-67) inhibits Na+ transport by inhibiting the Na+-K+-ATPase of IMCD cells, an effect mediated by the generation of PGE2.