title: The effects of adenosine on transepithelial resistance and sodium uptake in the inner medullary collecting duct.
abstract: 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+ reabsorption. 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 epithelium from rat kidney was grown in primary culture as a confluent monolayer on Costar filters, allowing selective access to the basolateral and apical surfaces of the cells. Transepithelial resistance was taken as a measure of epithelial permeability and ion conductance. Na+ uptake was studied using 22Na+ and used to determine the permeability of the epithelial monolayer specifically to Na+. Exposure of the basolateral aspect of the monolayer to adenosine (10(-8)-10(-7) M) increased 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/cm2. 1,3-Dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX, 5 x 10(-9) M), an adenosine antagonist with selectivity for the A1 receptor, inhibited the rise in transepithelial resistance and the decrease in Na+ uptake following the addition of adenosine. The effects of adenosine on transepithelial resistance were reproduced with the A1 receptor selective adenosine analogue N6-cyclohexyladenosine (CHA, 10(-8)-10(-7) M) but not with the A2 selective analogues, 5'-N-ethylcarboxamidoadenosine (NECA) or CGS 21680. CHA (10(-7) M) inhibited apical Na+ uptake by 50%, an effect abolished by PACPX. (ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Renal Physiology and Cell Biology Laboratory, Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University, Israel.
authors.forename: C
authors.initials: C
authors.lastname: Yagil
authors.forename: G
authors.initials: G
authors.lastname: Katni
authors.forename: Y
authors.initials: Y
authors.lastname: Yagil
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D018047:Receptors, Purinergic P1; D015222:Sodium Channels; D000584:Amiloride; D000241:Adenosine