title: Adenosine-stimulated Ca2+ reabsorption is mediated by apical A1 receptors in rabbit cortical collecting system.
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 A2 receptor, the A2 agonist CGS-21680 did not stimulate Ca2+ transport, while readily increasing cAMP. By contrast, the A1 agonist N6-cyclopentyladenosine (CPA) maximally stimulated Ca2+ transport without significantly affecting cAMP. Adenosine-stimulated transport was effectively inhibited by the A1 antagonist 1,3-dipropyl-8-cyclopenthylxanthine but not the A2 antagonist 3,7-dimethyl-1-propargylxanthine, providing additional evidence for the involvement of an A1 receptor. 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 A1 receptor to stimulate Ca2+ transport via a hitherto unknown pathway that does not involve cAMP formation, PKC activation, and/or Ca2+ mobilization.
authors.affiliation: Department of Biochemistry, University of Nijmegen, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: A
authors.initials: A
authors.lastname: Hartog
authors.forename: P H
authors.initials: PH
authors.lastname: Willems
authors.forename: R J
authors.initials: RJ
authors.lastname: Bindels
mesh_terms: D000042:Absorption / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*
chemical_list: D018047:Receptors, Purinergic P1; D000241:Adenosine; D002118:Calcium