title: Potentiation of [Ca2+]i response to angiotensin III by cAMP in cortical thick ascending limb.
abstract: BACKGROUND
  In the rat cortical thick ascending limb (CTAL), intracellular Ca2+ ([Ca2+]i) responses to angiotensin II (Ang II) and angiotensin III (Ang III) were mediated by the Ang II subtype 1A receptor (AT1A-R), whereas the arginine vasopressin (AVP)-dependent cAMP accumulation involved the vasopressin receptor type 2 (V2-R). This work was performed in CTAL to investigate the crosstalk between these two receptors by studying their transduction pathways.
  
  
  METHODS
  The cAMP-dependent pathway was activated by 10 minutes of prestimulation with either forskolin, CTP-cAMP or AVP, and Ang II/Ang III-induced [Ca2+]i responses were assessed.
  
  
  RESULTS
  Pretreatment with 5 micromol/L forskolin significantly enhanced the [Ca2+]i response induced by 10-7 mol/L either Ang II or Ang III. Analysis of dose-response curves to Ang III in forskolin-treated CTAL demonstrated that the maximal [Ca2+]i response was significantly increased without altering the EC50. In Ca2+-free medium, the forskolin-induced potentiation of the [Ca2+]i response to Ang III was weaker but always present, suggesting that this effect was not only due to intracellular Ca2+ release but also to extracellular Ca2+ influx. Furthermore, the fact that the forskolin-induced potentiation of the [Ca2+]i response to Ang III was blocked by 10 micromol/L H-89, a specific protein kinase A (PKA) inhibitor, indicated that this effect occurred via activation of PKA. Finally, the potentiation of the [Ca2+]i response to Ang III also was observed following pretreatment with 100 micromol/L CTP-cAMP or 10-7 mol/L AVP.
  
  
  CONCLUSIONS
  In CTAL, there is a positive crosstalk between the adenylyl cyclase and phosphoinositide pathways mediated by V2- and AT1A-R, respectively, through activation of PKA.
authors.affiliation: INSERM U 36, Collège de France and INSERM U 367, Paris, France.
authors.forename: Annette
authors.initials: A
authors.lastname: Hus-Citharel
authors.forename: Jeannine
authors.initials: J
authors.lastname: Marchetti
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Catherine
authors.initials: C
authors.lastname: Llorens-Cortes
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007672:Kidney Cortex; D008138:Loop of Henle / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000805:Angiotensin III; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019808:Losartan; D002118:Calcium