title: Vasopressin-induced activation of protein kinase C in renal epithelial cells.
abstract: Recent studies indicate that the actions of arginine vasopressin (AVP) and other agonists that stimulate electrogenic sodium transport in renal epithelial A6 cells are linked to a Ca(2+)-mobilizing signal transduction mechanism that involves generation of inositol trisphosphate. Since diacylglycerol is the other product in this pathway, studies were performed to determine the possible role of PKC in the stimulation of sodium transport. AVP induced a biphasic increase in diacylglycerol generation, characterized by an initial rapid rise and then a sustained elevation, and PKC activation, reflected by phosphorylation of a specific 80 kDa myristoylated alanine-rich PKC substrate (MARCKS). To determine the PKC isoform(s) involved in this process, immunoblot analysis was performed using antisera that recognize both classical PKC isoforms, XPKC-I and XPCK-II, cloned from Xenopus oocytes. The transcripts of both isoforms were expressed in the A6 cell. Since protein recognized by antisera was translocated from cytosol to the particulate fraction after exposure to AVP, one or both isoforms were activated in the A6 cell. Further studies showed that cyclohexyladenosine and insulin, additional agonists of sodium transport in A6 cells, also stimulated phosphorylation of MARCKS. These results argue that Ca(2+)-dependent PKC is involved in the action of AVP, and that of other agonists, which stimulate sodium transport.
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ali
authors.forename: S
authors.initials: S
authors.lastname: Kantachuvesiri
authors.forename: J I
authors.initials: JI
authors.lastname: Smallwood
authors.forename: L J
authors.initials: LJ
authors.lastname: Macala
authors.forename: C
authors.initials: C
authors.lastname: Isales
authors.forename: J
authors.initials: J
authors.lastname: Ji
authors.forename: R
authors.initials: R
authors.lastname: Reilly
authors.forename: J P
authors.initials: JP
authors.lastname: Hayslett
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012076:Renal Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D004075:Diglycerides; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D011506:Proteins; D012076:Renal Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; C027513:N(6)-cyclohexyladenosine; D011493:Protein Kinase C; D000241:Adenosine