THE EFFECTS OF ADENOSINE ON TRANSEPITHELIAL RESISTANCE AND SODIUM UPTAKE IN THE INNER MEDULLARY COLLECTING DUCT

It has been previously demonstrated that adenosine induces natriuresis when administered directly into the renal circulation of the rat. It was postulated that the mechanism was inhibition of tubule Na+ reabsor ption. In the current study, the hypothesis was tested that adenosine inhibits ion reabsorption across the inner medullary collecting duct ( IMCD), a tubule segment which is rich in adenosine receptors. IMCD epi thelium from rat kidney was grown in primary culture as a confluent mo nolayer on Costar filters, allowing selective access to the basolatera l and apical surfaces of the cells. Transepithelial resistance was tak en as a measure of epithelial permeability and ion conductance. Na+ up take was studied using Na-22(+), and used to determine the permeabilit y of the epithelial monolayer specifically to Na+. Exposure of the bas olateral aspect of the monolayer to adenosine (10(-8) - 10(-7) M) incr eased transepithelial resistance in a dose- and time-dependent manner; in parallel, adenosine (10(-7) - 10(-6) M) reduced apical Na+ uptake from 20+/-5 to 10+/-2 nmol/cm(2). 1,3-Dipropyl-8-(2-amino-4-chlorophen yl)-xanthine (PACPX, 5x10(-9) M), an adenosine antagonist with selecti vity for the A(1) receptor, inhibited the rise in transepithelial resi stance and the decrease in Na+ uptake following the addition of adenos ine. The effects of adenosine on transepithelial resistance were repro duced with the A(1) receptor selective adenosine analogue N-6-cyclohex yladenosine (CHA, 10(-8) - 10(-7) M) but not with the A(2) selective a nalogues, 5'-N-ethylcarboxamidoadenosine (NECA) or CGS 21680. CHA (10( -7) M) inhibited apical Na+ uptake by 50%, an effect abolished by PACP X. The effects of adenosine on transepithelial resistance and Na+ upta ke were inhibited, but only in part, by amiloride. These data suggest that adenosine inhibits ion movement, specifically apical Na+ uptake, across the IMCD epithelium and that this effect is mediated by A(1) re ceptors from the basolateral aspect of the cell. The results are consi stent with the hypothesis that adenosine inhibits Na+ reabsorption acr oss the IMCD.