Vasopressin-stimulated electrogenic sodium transport in A6 cells is linked to a Ca(2+)-mobilizing signal mechanism.
Vasopressin is known to activate two types of cell surface receptors; V2, coupled to adenylate cyclase, and V1, linked to a Ca(2+)-dependent transduction system. We investigated whether arginine vasopressin (AVP) stimulation of electrogenic sodium transport in A6 cells, derived from Xenopus laevis, is mediated by activation of either one or both types of AVP-specific receptors. AVP caused a rapid increase in electrogenic sodium transport, reflected by the transepithelial potential difference (VT) and equivalent short circuit current (Ieq) measurements. AVP also rapidly increased intracellular Ca2+ (Ca2+i) and total inositol trisphosphate. The increase in Ieq was dependent on the rise in (Ca2+i), because 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) dose-dependently inhibited the Ieq response. There was no evidence, however, that activation of adenylate cyclase mediated AVP-stimulated Ieq; transport was not inhibited after AVP-induced activation of adenylate cyclase was abolished by 2',5'-dideoxyadenosine or when cAMP-dependent protein kinase (PKA) activity was abolished by the specific PKA inhibitor IP20. Further studies showed that although both forskolin and 8-(4-chlorophenylthio)-cAMP stimulated Ieq, this occurred by mechanisms independent of PKA activation. These results indicate that AVP-stimulated Na+ transport is mediated by a V1 receptor and a Ca(2+)-dependent mechanism.
Hayslett
J P
JP
Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Macala
L J
LJ
Smallwood
J I
JI
Kalghatgi
L
L
Gassala-Herraiz
J
J
Isales
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D017483:Receptors, Vasopressin / Q000378:metabolism*; D015290:Second Messenger Systems; D012964:Sodium / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D014867:Water / Q000378:metabolism; D014982:Xenopus laevis
D007295:Inositol Phosphates; D017483:Receptors, Vasopressin; D013873:Thionucleotides; D014867:Water; D001127:Arginine Vasopressin; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004533:Egtazic Acid; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium