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- Title
Potentiation of [Ca[sup 2+] ][sub i] response to angiotensin III by cAMP in cortical thick ascending limb.
- Authors
Hus-Citharel, Annette; Marchetti, Jeannine; Corvol, Pierre; Llorens-Cortes, Catherine
- Abstract
Background. In the rat cortical thick ascending limb (CTAL), intracellular Ca[sup 2+] ([Ca[sub 2+]][sub i]) responses to angiotensin II (Ang II) and angiotensin III (Ang III) were mediated by the Ang II subtype 1A receptor (AT[sub 1A]-R), whereas the arginine vasopressin (AVP)-dependent cAMP accumulation involved the vasopressin receptor type 2 (V[sub 2]-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 [Ca[sub 2+]][sub i] responses were assessed. Results. Pretreatment with 5 µmol/L forskolin significantly enhanced the [Ca[sub 2+]][sub i] response induced by 10[sub -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 [Ca[sub 2+]][sub i] response was significantly increased without altering the EC[sub 50]. In Ca[sup 2+]-free medium, the forskolin-induced potentiation of the [Ca[sup 2+]][sub i] response to Ang III was weaker but always present, suggesting that this effect was not only due to intracellular Ca[sup 2+] release but also to extracellular Ca[sup 2+] influx. Furthermore, the fact that the forskolin-induced potentiation of the [Ca[sup 2+]][sub i] response to Ang III was blocked by 10 µmol/L H-89, a specific protein kinase A (PKA) inhibitor, indicated that this effect occurred via activation of PKA. Finally, the potentiation of the [Ca[sup 2+]][sub i] response to Ang III also was observed following pretreatment with 100 µmol/L CTP-cAMP or 10[sup -7] mol/L AVP. Conclusions. In CTAL, there is a positive crosstalk between the adenylyl cyclase and phosphoinositide pathways mediated by V[sub 2]- and AT[sub 1A]-R, respectively, through activation of PKA.
- Subjects
CALCIUM; ANGIOTENSINS; ADENOSINE monophosphate
- Publication
Kidney International, 2002, Vol 61, Issue 6, p1996
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00366.x