Adenosine-stimulated Ca2+reabsorption is mediated by apical A1receptors in rabbit cortical collecting system

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Abstract
Confluent monolayers of immunodissected rabbit connecting tubule and cortical collecting duct cells, cultured on permeable supports, were used to study the effect of adenosine on net apical-to-basolateral Ca2+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 A2receptor, the A2agonist CGS-21680 did not stimulate Ca2+transport, while readily increasing cAMP. By contrast, the A1agonist N6-cyclopentyladenosine (CPA) maximally stimulated Ca2+transport without significantly affecting cAMP. Adenosine-stimulated transport was effectively inhibited by the A1antagonist 1,3-dipropyl-8-cyclopenthylxanthine but not the A2antagonist 3,7-dimethyl-1-propargylxanthine, providing additional evidence for the involvement of an A1receptor. Both abolishment of the adenosine-induced transient increase in intracellular Ca2+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 Ca2+transport. The data presented suggest that adenosine interacts with an apical A1receptor to stimulate Ca2+transport via a hitherto unknown pathway that does not involve cAMP formation, PKC activation, and/or Ca2+mobilization.