title: Hormone-stimulated Ca2+ transport in rabbit kidney: multiple sites of inhibition by exogenous ATP.
abstract: Exogenous ATP markedly reduced 1-desamino-8-D-arginine vasopressin (dDAVP)-stimulated Ca2+ transport and cAMP accumulation in primary cultures of rabbit connecting tubule and cortical collecting duct cells. Similarly, ATP inhibited the stimulatory effect of 8-bromo-cAMP. At first sight, this is in agreement with the "classic" concept that dDAVP exerts its stimulatory effect via cAMP. However, dDAVP-stimulated Ca2+ transport was markedly reduced by the protein kinase C (PKC) inhibitor chelerythrine, reported previously to inhibit the cAMP-independent pathway responsible for parathyroid hormone-, [Arg8]vasopressin-, PGE2-, and adenosine-stimulated Ca2+ transport. Chelerythrine also inhibited the increase in Ca2+ transport evoked by the cAMP-independent A1 receptor agonist N6-cyclopentyladenosine (CPA). Downregulation of phorbol ester-sensitive PKC isoforms by chronic phorbol ester treatment has been shown before to be without effect on hormone-stimulated Ca2+ transport, indicating that the chelerythrine-inhibitable pathway consists of a phorbol ester-insensitive PKC isoform. Here, this maneuver did not affect ATP inhibition of dDAVP-stimulated Ca2+ transport and cAMP formation, while abolishing ATP inhibition of CPA-stimulated Ca2+ transport. These findings show that ATP acts via 1) a phorbol ester-sensitive PKC isoform to inhibit hormonal stimulation of Ca2+ transport at the level of the chelerythrine-inhibitable pathway involving a phorbol ester-insensitive PKC isoform and 2) a phorbol ester-insensitive mechanism to inhibit V2 receptor-mediated concomitant activation of this pathway and adenylyl cyclase.
authors.affiliation: Department of Cell Physiology, University of Nijmegen, 6500 HB Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Baal
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: M
authors.initials: M
authors.lastname: Groenendijk
authors.forename: C H
authors.initials: CH
authors.lastname: van Os
authors.forename: R J
authors.initials: RJ
authors.lastname: Bindels
authors.forename: P H
authors.initials: PH
authors.lastname: Willems
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000470:Alkaloids; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D010617:Phenanthridines; D058915:Purinergic P1 Receptor Antagonists; D001127:Arginine Vasopressin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C048599:N(6)-cyclopentyladenosine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; C016299:chelerythrine; D011493:Protein Kinase C; D003894:Deamino Arginine Vasopressin; D000241:Adenosine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D007213:Indomethacin