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+ 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)
Yagil
C
C
Renal Physiology and Cell Biology Laboratory, Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University, Israel.
Katni
G
G
Yagil
Y
Y
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*
D018047:Receptors, Purinergic P1; D015222:Sodium Channels; D000584:Amiloride; D000241:Adenosine