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, 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.
Hoenderop
J G
JG
Department of Biochemistry, University of Nijmegen, The Netherlands.
Hartog
A
A
Willems
P H
PH
Bindels
R J
RJ
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*
D018047:Receptors, Purinergic P1; D000241:Adenosine; D002118:Calcium