ADENOSINE-STIMULATED CA2+ REABSORPTION IS MEDIATED BY APICAL A(1) RECEPTORS IN RABBIT CORTICAL COLLECTING SYSTEM

Confluent monolayers of immunodissected rabbit connecting tubule and c ortical collecting duct cells, cultured on permeable supports, mere us ed to study the effect of adenosine on net apical-to-basolateral Ca2transport. Apical, but not basolateral, adenosine increased this trans port dose dependently from 48 +/- 3 to 110 +/- 4 nmol.h(-1).cm(-2). Al though a concomitant increase in cAMP formation suggested the involvem ent of an A(2) receptor, the A(2) agonist CGS-21680 did not stimulate Ca2+ transport, while readily increasing cAMP. By contrast, the A(1) a gonist N-6-cyclopentyladenosine (CPA) maximally stimulated Ca2+ transp ort without significantly affecting cAMP. Adenosine-stimulated transpo rt was effectively inhibited by the A(1) antagonist 1,3-dipropyl-8-cyc lopenthylxanthine but not the A(2) antagonist 3,7-dimethyl-1-propargyl xanthine, providing additional evidence for the involvement of an A(1) receptor. Both abolishment of the adenosine-induced transient increas e in intracellular Ca2+ concentration by ,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 adenosin e-stimulated Ca2+ transport. The data presented suggest that adenosine interacts with an apical A(1) receptor to stimulate Ca2+ transport vi a a hitherto unknown pathway that does not involve cAMP formation, PKC activation, and/or Ca2+ mobilization.