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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Hus-Citharel A,Marchetti J,Corvol P,Llorens-Cortes C

doi

10.1046/j.1523-1755.2002.00366.x

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

1996-2005

issue

6

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)48449-2

journal_volume

61

pub_type

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