Adenosine-stimulated Ca2+ reabsorption is mediated by apical A1 receptors in rabbit cortical collecting system

Confluent monolayers of immunodissected rabbit connecting tubule and cortical collecting duct cells, cultured on permeable supports, mere used to study the effect of adenosine on net apical-to-basolateral Ca(2+) transport. Apical, but not basolateral, adenosine increased this transport dose dependently from 48 +/- 3 to 110 +/- 4 nmol.h(-1).cm(-2). Although a concomitant increase in cAMP formation suggested the involvement of an A(2) receptor, the A(2) agonist CGS-21680 did not stimulate Ca(2+) transport, while readily increasing cAMP. By contrast, the A(1) agonist N(6)-cyclopentyladenosine (CPA) maximally stimulated Ca(2+) transport without significantly affecting cAMP. Adenosine-stimulated transport was effectively inhibited by the A(1) antagonist 1,3-dipropyl-8-cyclopenthylxanthine but not the A(2) antagonist 3,7-dimethyl-1-propargylxanthine, providing additional evidence for the involvement of an A(1) receptor. Both abolishment of the adenosine-induced transient increase in intracellular Ca(2+) concentration by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and downregulation of protein kinase C (PKC) by prolonged phorbol ester treatment were without effect on adenosine-stimulated Ca(2+) transport. The data presented suggest that adenosine interacts with an apical A(1) receptor to stimulate Ca(2+) transport via a hitherto unknown pathway that does not involve cAMP formation, PKC activation, and/or Ca(2+) mobilization.