Premium
Variability in the strength of AT 1 R Ca 2+ signaling
Author(s) -
Scott Lena,
Bernhem Kristoffer,
Brismar Hjalmar,
Aperia Anita
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.903.6
Subject(s) - nifedipine , desensitization (medicine) , angiotensin ii , chemistry , endocrinology , medicine , renin–angiotensin system , receptor , calcium , blood pressure , dose dependence , pharmacology
The renin angiotensin system is a principal physiological regulatory system for blood pressure and the Angiotensin type 1 receptor (AT 1 R) is an important target for treatment of hypertension. Using AT 1 R expressing HEK293a cells we study the Ca 2+ response to repeated doses of physiological, 1 nM [Ang II] and pharmacological, 100 nM [Ang II] at 0, 7 and 37 min. AT 1 R activation results in Ca 2+ release from intracellular stores. AT 1 R signaling has typically been studied at pharmacological 100 nM [Ang II]. At 100 nM [Ang II] a significant desensitization was seen in response to the 2nd dose with partial recovery observed at the 3rd dose. Mean Δ [Ca 2+ ] i was 150, 30 and 70 nM respectively. At 1 nM [Ang II] no desensitization was observed between the first two doses, both at 15 nM, and the response to the 3rd dose, 40 nM, is significantly increased. As recent studies suggest a crosstalk between AT 1 R and Voltage Gated Calcium Channels, we also studied the effect of blocking Ca 2+ channels with Nifedipine, therapeutically used in hypertension treatments, on AT 1 R response. No change to basal [Ca 2+ ] was seen in presence of Nifedipine, whilst an increase was found in Ca 2+ response from repeated doses of 1 nM [Ang II], 130, 110 and 80 nM. The same trend was seen in Podocyte enriched primary cultures. In summary this study shows novel aspects to the AT 1 R signaling modulation with implications for the treatment of hypertension.